IntroductionMyeloid cells play a critical role in the pathogenesis of Inflammatory Bowel Diseases (IBDs), including Ulcerative Colitis (UC) and Crohn’s Disease (CD). Dysregulation of the JAK/STAT pathway is associated with many pathological conditions, including IBD. Suppressors Of Cytokine Signaling (SOCS) are a family of proteins that negatively regulate the JAK/STAT pathway. Our previous studies identified that mice lackingSocs3in myeloid cells developed a hyper-activated phenotype of macrophages and neutrophils in a pre-clinical model of Multiple Sclerosis.MethodsTo better understand the function of myeloid cellSocs3in the pathogenesis of colitis, mice withSocs3deletion in myeloid cells (Socs3ΔLysM) were utilized in a DSS-induced colitis model.ResultsOur results indicate thatSocs3deficiency in myeloid cells leads to more severe colitis induced by DSS, which correlates with increased infiltration of monocytes and neutrophils in the colon and increased numbers of monocytes and neutrophils in the spleen. Furthermore, our results demonstrate that the expression of genes related to the pathogenesis and diagnosis of colitis such asIl1β,Lcn2,S100a8andS100a9were specifically enhanced inSocs3-deficient neutrophils localized to the colon and spleen. Conversely, there were no observable differences in gene expression in Ly6C+monocytes. Depletion of neutrophils using a neutralizing antibody to Ly6G significantly improved the disease severity of DSS-induced colitis inSocs3-deficient mice.DiscussionThus, our results suggest that deficiency ofSocs3in myeloid cells exacerbates DSS-induced colitis and thatSocs3prevents overt activation of the immune system in IBD. This study may provide novel therapeutic strategies to IBD patients with hyperactivated neutrophils.