Understanding the effect of Chemokine signalling on the Immunometabolism of Dendritic Cells

Abstract

Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) in the immune system that capture antigens and present to the naïve T cells through their MHC class presentation to develop an effector immune response against them. DCs also express some co-stimulatory molecules and secrete specific cytokines that aid in the differentiation of the T cells in their microenvironments. Upon antigen recognition, DCs undergo maturation, increasing their CD40 expression along with the co-stimulatory molecules like CD80, CD86, MHC-II and MHC-I. DCs are present throughout the body, capture antigens, and migrate to the nearby lymphoid tissues, where they present antigens to orchestrate the immune responses. Such migrations are promoted by specific chemokine molecules. Thymus expressed Chemokine (TECK) or CC- Chemokine Ligand 25 (CCL25) is a well-known chemokine secreted by thymic epithelial cells (TECs) and intestinal epithelial cells that acts as a chemoattractant for the CC-Chemokine Receptor 9 (CCR9) expressing immune cells such as T cells, Dendritic cells (DCs), etc. towards its gradient. Some basal level expression of CCL25 is maintained to maintain the thymus and gut homeostasis, in which CCR9+ DCs are assumed to play an important role since they are crucial for maintaining peripheral tolerance. It has been found that CCR9+ DCs induce Treg formation when cultured with the naïve CD4+Tcells. Also, they induce Th1 and Th17 differentiation during inflammatory conditions. However, their origin, functions, and downstream elements in the CCR9-CCL25 axis are unknown. As CCR9+Cells are abundantly present in thymus, we have studied the thymic microenvironmental factors responsible for the tolerance and autoimmunity in CCR9-/-thymus compared to wild-type using Mass Spectrometry. We have also studied the immunophenotype of dendritic cell line, DC2.4, upon CCL25 stimulation as well as during CCR9 upregulation.