**IL36G Gene Overview:**

The IL36G gene encodes a member of the interleukin 1 cytokine family, particularly recognized for its role in mediating immune and inflammatory responses. It belongs to a cluster of cytokine genes on chromosome 2 and is primarily associated with skin and epithelial barrier responses, especially in keratinocytes, dendritic cells, and T-cells.

### 1. Other Genes Associated with IL36G

- **IL1RL2 (Interleukin 1 receptor-like 2):** Functions as the receptor for the IL-36 cytokines, including IL-36γ (the protein encoded by IL36G).
- **IL1F5 (Interleukin 1 family, member 5):** Acts as an inhibitor of IL-36 signaling.
- **IL1B (Interleukin 1, beta):** A key pro-inflammatory cytokine that can stimulate the expression of IL36G.
- **IL1RAP (Interleukin 1 receptor accessory protein):** Works together with IL-36 and other interleukin-1 family members in signaling mechanisms.
- **TNF (Tumor Necrosis Factor):** Can indirectly influence the expression levels of IL36G as part of inflammatory responses.
- **STAT3 (Signal Transducer and Activator of Transcription 3):** Has been indicated in pathways influenced by IL-36 signaling, typically related to inflammation.
- Other chemokines and cytokines, including IL-8 and other CCL family members mentioned in the summary, participate in pathways activated by IL36G.

### 2. Aging and Age-Related Diseases

Although direct studies specifically targeting IL36G in aging are limited, a couple of associations can be made:

- **Chronic Inflammation:** IL-36 signaling is involved in pro-inflammatory conditions, which are generally heightened in aging. Chronic inflammation is often referred to as "inflammaging" and has been implicated in numerous age-related diseases like Alzheimer’s disease and cardiovascular diseases.
- **Autoimmune Conditions:** Elevated IL-36 levels have been noted in conditions such as psoriasis and other skin inflammatory disorders, which can have increased prevalence with age.
- **Cancer:** Research has indicated that the IL-36 cytokine family may play a role in tumor microenvironments and may influence tumor progression in various cancers, particularly in immune-related responses in older adults.

### 3. Drugs or Drug Classes Interacting with IL36G

- **Corticosteroids:** These are commonly used anti-inflammatory drugs that can inhibit the expression of pro-inflammatory cytokines, including cytokines of the IL-1 family such as IL-36.
- **Biologic Therapies:** Current treatments for autoimmune disorders (like psoriasis), especially those targeting inflammatory pathways (e.g. TNF inhibitors and IL-17 inhibitors), might influence the IL-36 signaling pathway; however, specific IL36G-targeted therapies are still under investigation.
- **Immunosuppressants:** Medications that modulate the immune response may also impact IL-36 signaling pathways indirectly.

### 4. Pathways and Biological Processes

IL36G is involved in several key pathways and biological processes:

- **Cytokine Signaling Pathway:** Acts primarily through the IL1RL2/IL-36R receptor, activating downstream NF-kappa-B and MAPK signaling pathways.
- **Inflammatory Response:** Specifically involved in the local inflammatory response, acting to amplify pro-inflammatory signals in tissues during immune activation.
- **Innate Immune Response:** Modulates responses to various pathogens, including fungal infections.
- **Cellular Processes:** Promotion of keratinocyte proliferation, maturation of dendritic cells, and driving infiltration of immune cells (such as macrophages and neutrophils) into tissues.
- **Chemokine Production:** Stimulates the expression of chemokines critical for recruiting immune cells to sites of inflammation.

In conclusion, IL36G plays a critical role in mediating inflammatory responses, particularly in the skin and respiratory system, with implications for understanding its function in aging and disease contexts.