IL7Rα and TSLPR expression on Langerhans cells in response to inflammatory stimulation

Abstract A key component of immune barriers are innate immune cells localized in the epithelium responsible for sensing local signals such as foreign antigens and cytokines. In the skin, specialized antigen presenting cells (APC) known as Langerhans cells (LC) can integrate these signals influencing downstream T cell activation and polarization. Thymic stromal lymphopoietin (TSLP) is a proinflammatory mediator released by keratinocytes that promotes LC to enhance type 2 immune response (Th2). When Th2 response becomes unbalanced, it induces type 2 inflammation as seen in atopic dermatitis. TSLP signaling is regulated by two cell surface receptor chains: TSLP receptor (TSLPR) and IL7Rα. Interestingly, IL7Rα is not commonly expressed in murine conventional APC such as dendritic cells (DC). Our previous findings have shown that IL7Rα expression regulates TSLP sensitivity of splenic DCs (sDC) ex vivo. However, the receptor expression dynamic in tissue resident LC and its biological implications has not yet been elucidated. In this study we enriched LC from healthy mice B6 mice using MACS magnetic beads. Cytokine surface receptors and pospho-STAT5 activation were assessed using flow cytometry. Moreover, topic administration of vitamin analog MC903 will be used to evaluate TSLPR and IL7Rα dynamic. Our current results indicate that IL7Rα is expressed on unstimulated LC contrary to sDC. Furthermore, TSLPR was not differently expressed between LC and sDC. Functional assessment of p-STAT5 ex vivo and the dynamic of these receptors in the context of MC903 treatment in vivo is yet to be measured. Our results suggest that tissue resident APC regulate differently cytokines receptors enabling spatial-temporal regulation of proinflammatory signals. Academy of Finland (IJ: grants: 25013080481 and 25013142041), The Competitive State Research Financing of the Expert Responsibility Area of Fimlab Laboratories (grant X51409 to IJ), Tampere University Hospital Support Foundation (IJ) and Tampere Tuberculosis Foundation (IJ).