expression in myeloid cells modulates the pathogenesis of dextran sulfate sodium (DSS)-induced colitis.

Introduction: Myeloid 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 lacking in myeloid cells developed a hyper-activated phenotype of macrophages and neutrophils in a pre-clinical model of Multiple Sclerosis.

Methods: To better understand the function of myeloid cell in the pathogenesis of colitis, mice with deletion in myeloid cells ( ) were utilized in a DSS-induced colitis model.

Results: Our results indicate that deficiency 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 as , , and were specifically enhanced in -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 in -deficient mice.

Discussion: Thus, our results suggest that deficiency of in myeloid cells exacerbates DSS-induced colitis and that prevents overt activation of the immune system in IBD. This study may provide novel therapeutic strategies to IBD patients with hyperactivated neutrophils.