*The Psychoanalytic Crisis: The Place of Ego in a Contemporary World DOI: http://dx.doi.org/10.5772/intechopen.107249*

justified in the name of health, which favors insurance programs and at the same time brings "normalization" to the diagnostic. According to the new criteria of DSM-V, the gender dysphoria can be defined as: "a strong desire to be free from one's primary and/or secondary sexual characteristics, because of a marked incongruence with one's expierience/ expressed gender," and "a strong desire to be of the other gender" and additionally "a strong conviction that one has the typical feelings and reaction of the other gender." Besides that, it also states that "is associated with clinically significant impairment in social, occupational, or other important areas of functioning" [49].

The diagnostic changes mark a medical effort in medicalizing the transssexualiy and consequently proposing a way to treat it. From that idea that the gender nature has to do with something subjective and from a symbolic order distorted, mischaracterizing the symbolic formation along the development with concepts that validate the normatization of transsexuality. Thus, in a rush to satisfy parents' wishes and their own medical service, an interruption of the physiological process is proposed in order to facilitate surgical procedure.

The case Bell versus Tavistock is an example of the new position that is rising against this diagnosis. In 2020, the British Court brings to question if children under 16 years old are able to decide by themselves if they can take hormones suppressants to facilitate in future the sex changing. This case was based on a patient from the Tavistock Clinic that decided with 16 years old to use suppressants and after the transition preferred to return to the biological gender. At last, the Britannic Justice decided that the children under 16 years old hardly have the competence to decide over the use of medication, modifying the conduct line that has been carried out by the only Britannic public health service that offers this treatment [50].

Some psychoanalysts critical to the vision that promotes hormone suppressants in children see the identity problem as requiring a symbolic work, and the body intervention is a mistake, a psychotic solution [51]. According to Bell [52], there are underexplored factors from a social point of view contributing to the current emergence regarding gender dysphoria that includes misogyny internalization, seeing patients as products, and social media influence.

From the epidemiologic point of view, the prevalence of gender dysphoria is from approximately 4.6:100.000 [53], and yet according to that reference there is no correlation with social status, intelligence, or ancestry. However, it is more common a transsexual transition from male to female (6.5%) than a female to male (2.6%), and for children, the literature states that the prevalence is from 1% to 4.7% [17].

Gender dysphoria is correlated to high taxes of affective disorders and anxiety (18–80%), personalities disorder (20–70%), suicidal tendencies, suicide, and selfharm. Consequently, gender dysphoria is a delicate diagnosis that needs extreme caution from development, once in children the gender incongruence fluctuates over time. Children that manifest gender dysphoria might feel comfortable 85% of the time with their gender after adolescence [54].

The Bell versus Tavistock case is a portrait of the crisis that psychoanalysis has been facing in relation to gender identity. Whereas a group is favoring a gender transition for subjects afflicted with the pathology, including the early interventions, another group became critical, as they understood and valued the search for a bigger understanding about symbolic processes from these subjects and how this suffering might indicate that there are other questions about Ego formation.

According to Sakteopoulou [55], the maintenance of children in a non-identity body creates a "massive gender trauma," which implies an emergence of a trauma from the gender dysphoric experience. What calls the attention is that according

to this author "some psychic conflicts cannot be resolved within the psychic realm, requiring action" [55], escaping from the analyst's place, that is in search for the subject psychic realm understanding, which implies, many times, in welcoming the anxiety lived in the analytical field.

Osserman and Wallerstein [50] assert that we are witnessing the growth of psychoanalytic literature that validates the access of teenagers and children to medical intervention, medication, and body mutilation, related to gender identity. This is an alert to the anxieties that emerge from analysts to countertransferential reactions.

Therefore, while on one side a group is *gender affirmative* and believes that the suffering by feeling in a body that is not their own is severe and so needs an early intervention, on the other side a group is *gender critical* and believes that the early intervention does not give time to explore another aspect that surrounds the identity formation of a child.

The defense of a neutral identity, in which the subject chooses what one's intend to be, for instance, it is offered to a child the "choose" of how one's want to be bodily recognized in the world, in a developmental moment that depends on environmental feedback to that end, in order to avoid the suffering that the reality principle brings also may affect the developmental process. According to Winnicott [56], a child is not born alone; therefore, it is a parent and caregiver's role to protect them, including in face of situations that require mature decisions about the child's life.

Afterward, it can be said that in order to avoid children's future suffering, these interventions could stop the development of the identity against inevitable traumas from life, that is, boundaries.


*Editorial* **Advances in the Molecular Mechanisms of Abscisic Acid and Gibberellins Functions in Plants**

**Víctor Quesada**

Instituto de Bioingeniería, Universidad Miguel Hernández, Campus de Elche, 03202 Elche, Spain<EMAIL_ADDRESS>Tel.: +34-96-665-8812

In this special issue entitled, "*Advances in the Molecular Mechanisms of Abscisic Acid and Gibberellins Functions in Plants*", eight articles are collected, with five reviews and three original research papers, which broadly cover different topics on the abscisic acid (ABA) field and, to a lesser extent, on gibberellins (GAs) research. These works explore ABA involvement in processes like flowering, plant defense, abiotic stress response or maturation of non-climacteric fruits, with reports in the last case of interplay between ABA and GAs. New findings on the regulation of ABA or GAs activity are also reported in this issue. The experimental studies and reviews published in this special issue focus on the results obtained using principally the plant model system *Arabidopsis thaliana*. Notwithstanding, other works based on agronomically important plants, such as grapevine or citrus species, are also included, and reveal the crucial role of ABA and GAs across different plant species. I summarize here the main findings of these works, which represent outstanding advances in our knowledge on the molecular mechanisms through which ABA and GAs control fundamental processes in plants.

Phytohormones GAs and ABA antagonistically regulate both plant growth and several developmental processes, such as seed maturation, seed dormancy, germination, hypocotyl elongation, primary root growth and flowering time. ABA and GAs generally inhibit and promote respectively cell elongation and growth, and the mutual antagonism between these two phytohormones governs many developmental decisions in plants [1].

In addition to the growing body of evidence for ABA as a modulator of plant growth and development [2], ABA is primarily known for being a fundamental player in the response, tolerance and adaptation of plants to diverse abiotic stress conditions, among which low temperatures, heat, drought, salinity or flooding are highlighted [3]. Interestingly, different recent works suggest a function for GAs in controlling some biological processes in response to stress [4–6].

This special issue "Advances in the Molecular Mechanisms of Abscisic Acid and Gibberellins Functions in Plants" contains eight articles; most of these focus on ABA, five are review articles and three are original research papers published by field experts. These manuscripts will help to understand the fundamental roles of GAs and ABA in the regulation of plant growth, development, and in responses to abiotic or biotic stresses. These articles will also shed light on the molecular mechanisms of ABA and GAs action in plants. The reviews published in this issue focus on the interaction between ABA and GAs in regulating non climacteric fruit development and maturation [7], current knowledge on the role of ABA in mediating mechanisms whereby grapevine deals with abiotic stresses [8], the analysis of the role of ABA in flowering transition [9], the mechanism by which the type 2C Protein Phosphatases (PP2C) gene transcription modulates ABA signaling [10], and the role of the Mediator complex on the ABA signaling pathway and abiotic stress response [11]. The original research articles investigate the causes and consequences of the kaolin-induced modulation of ABA biosynthesis in grapevines when faced with a water deficit [12], the involvement of ABA in plant immune responses [13], and the relation between GAs and Arabidopsis receptor-like cytoplasmic kinase (RLCK) VI\_A2 [14]. In this editorial, I summarize the main findings of these eight insightful works.

**Citation:** Quesada, V. Advances in the Molecular Mechanisms of Abscisic Acid and Gibberellins Functions in Plants. *Int. J. Mol. Sci.* **2021**, *22*, 6080. https://doi.org/ 10.3390/ijms22116080

Received: 25 May 2021 Accepted: 31 May 2021 Published: 4 June 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Fruit development and maturation results from an intricate interplay of molecular and physiological processes, regulated by endogenous (hormones) and external (environment) factors. The paper by Alferez et al. [7] exhaustively reviews the interplay between ABA and GAs in regulating the development and maturation of non-climacteric fruits at the molecular level, in economically important fruits like grape berries, strawberries and citruses. Alferez et al. [7] also relate the interaction of ABA and GAs with ethylene and sugar signaling in modulating non-climacteric fruit development and maturation. They depict a time-course model in which GA levels lower, ABA levels rise and ethylene production remains steady, whereas ethylene perception increases as non-climacteric fruit maturation progresses. Notwithstanding, Alferez et al. [7] also highlight that although current knowledge clearly points out the crosstalk between ABA and GAs as a major factor that controls fruit maturation, fine details of this regulation are still not well-understood and warrant further research. Finally, the authors examine the increasing body of evidence about ABA, GAs and the genus Citrus, which reveal that this woody genus can be considered an emerging plant model system for non-climacteric maturation studies.

Climate change poses a threat to important agricultural regions in the world, such as Mediterranean-climate areas, where socio-economically relevant crops (e.g., grapevine) can be seriously threatened. Consequently, improvements in viticulture techniques are needed, and better knowledge of grapevine physiology under stress conditions is required to achieve this. Besides its socio-economic importance, *Vitis vinifera* is also a model species in drought-response research. Marusig and Tombesi [8] provide an exhaustive overview of current knowledge on the role of ABA in mediating mechanisms whereby grapevines cope with abiotic stresses. In line with this, these authors especially focus on the mechanisms of ABA biosynthesis and translocation, the role of this phytohormone in regulating stomata closure and carbohydrates mobilization in response to drought stress, as well as ABA involvement in salt stress. The results of all these works clearly demonstrate that in *Vitis vinifera*, ABA is a key hormone involved in regulating the mechanisms for coping with major threats caused by climate change. Marusig and Tombesi [8] also highlight some main issues that deserve further research in this field, which are fundamentally the understanding of the role that ABA plays in drought stress in relation to water stress severity, duration and frequency, the interaction of ABA regulation and carbohydrates under water stress, and a profounder knowledge of the ABA function in the salt stress response.

Drought escape (DE), which is accelerated flowering that plants undergo in the vegetative phase in response to a water deficit, is considered an adaptive strategy for survival in dry climates. Studying DE in Arabidopsis has revealed that ABA plays a prominent role in controlling floral transition. The review by Martignago et al. [9] thoroughly explores current knowledge on how and in what spatial context ABA signals can affect the intricate floral network. These authors review ABA signaling and its multiple connections with the photoperiodic pathway, as the DE process is highly intertwined with photoperiodic genes, and integrating drought stimuli into the floral network is mediated largely by ABA. Martignago et al. [9] emphasize the important role of the *GIGANTEA* (*GI*) gene in integrating ABA signaling into flowering. *GI* is a key flowering gene required for photoperiod perception and clock function, and it also emerges as the key driver of DE. The current model suggests that the transcription factors (TFs) activated by ABA would recruit GI in different genomic positions to regulate gene networks involved in the drought stress response. These authors also analyze the putative role of FD and FD-like TFs in the modulation of ABA responses through interactions with FLOWERING LOCUS T (FT) and FT-like proteins at the shoot apex. Finally, Martignago et al. [9] discuss how the progress made in Arabidopsis about ABA-flowering molecular interactions can be transferred to crops. Along these lines, they highlight the utility of studying DE traits in natural populations, and the importance of rice as the DE pathway is essentially conserved in this species.

ABA plays a pivotal role in controlling plant stomata closure in response to osmotic stress, which prevents water loss. However even under stressful conditions, stomatal apertures occur to uptake CO2 for photosynthesis. Consequently, ABA levels must be very fine-tuned regulated to maintain plant homeostasis, which is achieved by controlling this hormone's biosynthesis, catabolism and signaling pathway. Jung et al. [10] comprehensively review how plants modulate the ABA signaling pathway by focusing on the transcriptional regulation of *PP2C* gene expression by ABA. They report that plant *PP2Cs* are a fundamental switch at the core of the ABA signaling network. Jung et al. [10] summarize the results hitherto published and demonstrate that ABA induces both repressors and activators of *PP2C* gene transcription to modulate ABA responses. These regulators can also affect the chromatin state by thereby regulating the transcription of ABA-responsive genes. Remarkably, this stress-induced chromatin remodeling state can be memorized, and even inherited, by the next generation of plants.

The Mediator is a conserved eukaryotic multiprotein complex that modulates the association between transcription factors and RNA-polymerase II to accurately regulate gene transcription. The functions of the Mediator complex in plant development processes and the biotic stress response have been extensively studied. However, its roles on the ABA signaling pathway and abiotic stress responses are still poorly known. Chong et al. [11] exhaustively summarize current knowledge on the regulatory roles of the Mediator complex on the ABA signaling pathway and in plant responses to three abiotic stresses: cold, high salinity and drought. These authors show that the Mediator complex is critical for plants to respond to abiotic stresses, and particularly focus on the participation of Mediator subunits MED16, MED18, MED25 and CDK8 in response to ABA and environmental cues. Chong et al. [11] report that Mediator subunits display multifunctional roles in salt and drought stress, and they discuss further potential research approaches needed to ascertain the role of the Mediator complex in regulating ABA and abiotic stress responses.

Kaolin is a natural clay used in some crops to alleviate the negative impact of extreme temperatures and/or drought on leaves and fruits, due to its light reflective properties. In line with this, a reduction in leaf ABA content associated with better leaf stomatal conductance induced by kaolin has been reported in grapevines. The research manuscript by Frioni et al. [12] explores the causes and consequences of not only the kaolin-induced modulation of ABA biosynthesis under progressive water shortage, but also the dynamic interactions between kaolin and ABA precursors violaxanthin (Vx), antheraxanthin (Ax), zeaxanthin (Zx) (representing the molecules involved in the xanthophyll (VAZ) cycle) and neoxanthin (Nx). Frioni et al. [12] report that kaolin, under water deficit, preserves leaf transpiration and reduces the accumulation of ABA in grapevine leaves by avoiding the deviation of the VAZ epoxidation/de-epoxidation cycle in the biosynthesis of Nx. Their findings contribute to explaining the mechanisms involved in the kaolin-induced protection of canopy functionality.

In addition to the aforementioned role of ABA in both controlling plant responses to abiotic stress and regulating plant developmental processes and growth, this hormone is also involved in responses to biotic stresses caused by a wide range of plant pathogens. ABA's role in plant pathogen response is complex, given its interplay with key players in defense (e.g., salicylic acid (SA), jasmonic acid (JA) and ethylene (ET)), and also because ABA outcomes depend on the biology of the infective pathogen. Furthermore, the specific receptor of ABA, which activates the positive or negative ABA responses during immune responses, has to date remained unknown. The comprehensive study by García-Andrade et al. [13] unveils a non-redundant role in plant immunity for one of the 14 multigene ABA receptor family members, namely ABA receptor PYRABACTIN RESISTANCE 1 (PYR1). This research manuscript reveals that this receptor is crucial for modulating the cross-talk between the SA and ET signaling pathways in plant defense. The results of García-Andrade et al. [13] also demonstrate that ABA-activated SNF1-related protein kinases (SnRKs) subfamily 2 (SnRK2s) are fundamental components for plant resistance to pathogens.

Valkai et al. [14] investigate the biological function of the Arabidopsis *RLCK VI\_A2* gene in the regulation of plant growth and skotomorphogenesis. RLCK VI\_A2 is a member of the plant-specific receptor-like cytoplasmic kinases (RLCKs) that form a large and barely

characterized family. The activity of the RLCK VI\_A class of dicots is regulated by Rho-ofplants (ROP) GTPases. Valkai et al. [14] show that loss of the *RLCK VI\_A2* function leads to reduced cell expansion and seedling growth. These mutant phenotypes can be rescued by the exogenous application of GAs. However, differences in neither GA content nor GA sensitivity of the *RLCK VI\_A2* defective mutant have been found compared to the wild type. An RNA-seq analysis indicated that the RLCK VI\_A2 kinase and GAs can act in parallel to regulate cell expansion and plant growth. Interestingly, the transcriptomic analysis also revealed a role for RLCK VI\_A2 kinase in cellular transport and cell wall organization.

Altogether, the contributions published in this special issue are excellent examples of the recent advances made in the molecular mechanisms of ABA and GA functions in plants. I wish to thank all the authors for their contributions and the reviewers for their critical assessments of these articles. I also thank the assistant editor Ms. Reyna Li for providing me with the opportunity to serve as the Guest Editor of this special issue.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The author declares no conflict of interest.

#### **References**


**6. Function of epithelial reticular cells**

Epithelial reticular cells, also called as TECs, are present both in the cortex and medulla; however, it can be easily recognizable in the thymic medulla through histology. These cells contained the thymic granules which is assumed to be the called as the thymic hormone [12]. This structure has the following functions;

The pluripotent progenitor cells migrated from the bone marrow to the thymus parenchyma, where the maturation of the unexperienced T cells occurs in the complex microarchitecture. However, this structure changes with the age.

### **7. Age associated changes occurs in the thymus**

Aging is an irreversible, on-going, and inevitable progression that is correlated through manifold organ dysfunction. The key organ of immune system and

**27**

being replaced by the stromal cells.

*Microarchitecture of the Thymus Gland; Its Age and Disease-Associated Morphological…*

primary organ of T cell production is the thymus gland which is endodermal in nature. Involution of the thymus with progressing age is into the consequences of a decreased T cell production primarily and leads toward a long list of the following diseases and even a mortality of the individual [6]. The corticomedullary junction is disrupted and the number of medullary epithelial cells are also decrease. This age-related cellular apoptosis and atrophy is still un-answered. There are several reasons to be considered for this process, but the main cause known is reactive oxygen species (ROS). The entity that are assumed to be responsible for expressing the age-related changes in the thymus is due to the discrepancy amongst the free oxygen-derived radicles and that of the antioxidants. Mitochondria is the main site were such reactive species are produced. Inside mitochondria, the oxidative stress produce ROS which results into mitochondrial damage within the cells and leads to liberate more ROS. In fact, aging is a physiological multifactorial process accompanied by decline of organ function. Histologically, the thymus gland of mammals divided into three consecutive morphological stages; the epithelial, the lymphopoietic, and the differentiated cellular microenvironment [7]. The progenitor cells are synthesizing in the thymus which later differentiated into mature T cells. Thymus also comprises the main stromal niche termed as thymic epithelial space. It supports T cell development and maturation [6]. The thymus is greater in size and is very dynamic in the neonates and pre-adolescents. With the progression in age, the involution starts and ultimately disappears and are then replaced by rudiments and fat. The process of involution started just after 1 year of birth [2]. If in case the thymus is absent in individual congenitally, then there would be a probable chance of deficiency of T cells. The main components of the thymus which undergoes involution during the aging include the T cells of hematopoietic origin and the TECs of non-hematopoietic origin. During the process of involution, disruption of the thymic epithelial/endothelial ratio happened and results into gradual loss of pro-T cells. Primarily just after the start of involution, the thymic epithelium mass is decreased in the parenchyma. This decrease in epithelium leads toward the disorganization of corticomedullary junction and results into loss of demarcation between the thymic cortex and medulla. This process where a continuous loss of cells and their functions is called aging [6]. Histology of thymus gland varies with the individual's age. It is observed that this gland is extremely delicate to stand against the biological abnormalities, for example, autoimmune diseases, infection, and age progression. It attains its maximum development shortly after birth. After attaining the age of puberty, the thymus gland regress and degenerate. Due to this effect the lymphocyte production decreases and the reticuloepithelial cells (thymic corpuscles) increases. Cellular portion, especially of T cell of thymus gland, decreases and are being replaced by connective tissue and adipose cells. Parenchyma of the thymus gland at and after puberty is filled with adipose tissue. Immunity, however, in this stage it is not compromised because progeny of the T lymphocytes has already been established. Thymus gland is well developed only in late fetal life and persists for a few months after birth [6]. Subsequent to this period, it undergoes rapid atrophy, fatty infiltration, and the amyloid degeneration [13]. Increase in the amount of adipose tissue and fat-bearing cells in the thymus parenchyma indicates that the body is now vulnerable to the infection and autoimmune diseases. So, in adult, only a thin remnant appeared in the anterior mediastinum or has entirely disappeared. Thymus gland size is also affected by the sex-steroid hormone and hypothalamic-pituitary-adrenal axes hormones [14]. It has been found that during the thymus involution, the CT which is present in the capsule, septa, perivascular tissue, and in the stroma of the cortex and medulla is getting enriched with the fibronectin contents. Later, most of the thymic parenchymal areas are

*DOI: http://dx.doi.org/10.5772/intechopen.88480*

#### *Microarchitecture of the Thymus Gland; Its Age and Disease-Associated Morphological… DOI: http://dx.doi.org/10.5772/intechopen.88480*

primary organ of T cell production is the thymus gland which is endodermal in nature. Involution of the thymus with progressing age is into the consequences of a decreased T cell production primarily and leads toward a long list of the following diseases and even a mortality of the individual [6]. The corticomedullary junction is disrupted and the number of medullary epithelial cells are also decrease. This age-related cellular apoptosis and atrophy is still un-answered. There are several reasons to be considered for this process, but the main cause known is reactive oxygen species (ROS). The entity that are assumed to be responsible for expressing the age-related changes in the thymus is due to the discrepancy amongst the free oxygen-derived radicles and that of the antioxidants. Mitochondria is the main site were such reactive species are produced. Inside mitochondria, the oxidative stress produce ROS which results into mitochondrial damage within the cells and leads to liberate more ROS. In fact, aging is a physiological multifactorial process accompanied by decline of organ function. Histologically, the thymus gland of mammals divided into three consecutive morphological stages; the epithelial, the lymphopoietic, and the differentiated cellular microenvironment [7]. The progenitor cells are synthesizing in the thymus which later differentiated into mature T cells. Thymus also comprises the main stromal niche termed as thymic epithelial space. It supports T cell development and maturation [6]. The thymus is greater in size and is very dynamic in the neonates and pre-adolescents. With the progression in age, the involution starts and ultimately disappears and are then replaced by rudiments and fat. The process of involution started just after 1 year of birth [2]. If in case the thymus is absent in individual congenitally, then there would be a probable chance of deficiency of T cells. The main components of the thymus which undergoes involution during the aging include the T cells of hematopoietic origin and the TECs of non-hematopoietic origin. During the process of involution, disruption of the thymic epithelial/endothelial ratio happened and results into gradual loss of pro-T cells. Primarily just after the start of involution, the thymic epithelium mass is decreased in the parenchyma. This decrease in epithelium leads toward the disorganization of corticomedullary junction and results into loss of demarcation between the thymic cortex and medulla. This process where a continuous loss of cells and their functions is called aging [6]. Histology of thymus gland varies with the individual's age. It is observed that this gland is extremely delicate to stand against the biological abnormalities, for example, autoimmune diseases, infection, and age progression. It attains its maximum development shortly after birth. After attaining the age of puberty, the thymus gland regress and degenerate. Due to this effect the lymphocyte production decreases and the reticuloepithelial cells (thymic corpuscles) increases. Cellular portion, especially of T cell of thymus gland, decreases and are being replaced by connective tissue and adipose cells. Parenchyma of the thymus gland at and after puberty is filled with adipose tissue. Immunity, however, in this stage it is not compromised because progeny of the T lymphocytes has already been established. Thymus gland is well developed only in late fetal life and persists for a few months after birth [6]. Subsequent to this period, it undergoes rapid atrophy, fatty infiltration, and the amyloid degeneration [13]. Increase in the amount of adipose tissue and fat-bearing cells in the thymus parenchyma indicates that the body is now vulnerable to the infection and autoimmune diseases. So, in adult, only a thin remnant appeared in the anterior mediastinum or has entirely disappeared. Thymus gland size is also affected by the sex-steroid hormone and hypothalamic-pituitary-adrenal axes hormones [14]. It has been found that during the thymus involution, the CT which is present in the capsule, septa, perivascular tissue, and in the stroma of the cortex and medulla is getting enriched with the fibronectin contents. Later, most of the thymic parenchymal areas are being replaced by the stromal cells.

*Thymus*

**4. Blood-thymus barrier**

**5. Maturation and selection of T cells**

**6. Function of epithelial reticular cells**

• It formed the blood-thymus barrier.

tor, interleukin, and interferon are secreted.

**7. Age associated changes occurs in the thymus**

It is a physical barrier formed by endothelial cells, epithelial reticular cells, and macrophages. Its function is to prevent developing lymphocytes from the exposure of blood borne antigen [8]. This barrier provides tremendous environment for the substance exchange between vasculature and the thymus also help maturation of the immature thymocytes. Macrophages present outside the capillaries prevent the interaction of the substances that are transported in the blood vessels with the developing T cells in the cortex. Matured T cells leave the thymus gland through the blood vessels and colonize in the lymph node, spleen, and lymphatic tissue of the organism [11].

Maturation is the condition of developing progenitor within the thymus parenchyma, where the cells known as thymocytes, undergoes various developmental processes to perform exclusively. These cells can be recognized based on manifestation of various markers on the cell surface and the antigen presenting cells present the T cells with self and foreign antigen [11]. It usually consists of positive selection in which the lymphocytes that recognize the foreign antigens survived and reached to the maturity then enter the medulla through the cortex. Later, goes to the other sites in the body via blood [9]. Maturation is a very complicated process and only a small number of lymphocytes reach to the stage of maturity in the thymus. The negative selection in which the lymphocytes which are incapable to distinguish the self-antigens are eliminated by the macrophages. This is approximately 95% of the total cells.

Epithelial reticular cells, also called as TECs, are present both in the cortex and medulla; however, it can be easily recognizable in the thymic medulla through histology. These cells contained the thymic granules which is assumed to be the called

• Secrete hormone which are required for proliferation, differentiation, and maturation of T cells. Also, for the expression of their surface markers. The hormones including thymulin, thymopoietin, thymosin, thymic numeral fac-

• It forms thymic (Hassall's) corpuscles, distinctive whorls, in the medulla of the thymus gland. The thymus gland is identified by this thymic corpuscle.

The pluripotent progenitor cells migrated from the bone marrow to the thymus

Aging is an irreversible, on-going, and inevitable progression that is correlated

parenchyma, where the maturation of the unexperienced T cells occurs in the complex microarchitecture. However, this structure changes with the age.

through manifold organ dysfunction. The key organ of immune system and

as the thymic hormone [12]. This structure has the following functions;

**26**