Epidermal expression of I-TAC (Cxcl11) instructs adaptive Th2-type immunity

To decipher early promoters of the local microenvironment for Th2-type immunity, we wanted to identify gene patterns that were induced by Leishmania major in the infected skin of susceptible, Th2-prone BALB/c, but not of resistant, Th1-prone C57BL/6 mice. We found a marked up-regulation of the chemokine I-TAC (Cxcl11) during the first 2 d of infection in the epidermis of susceptible but not of resistant mice. Accordingly, local injection of I-TAC (2×1 μg) in resistant mice on the first day of infection resulted in a Th2-driven, sustained deterioration of disease and dramatically enhanced parasite levels. On the cellular level, I-TAC decreased IL-12 production by dendritic cells (DCs) in skin-draining lymph nodes and by DCs in vitro. Thus, we demonstrate for the first time that epidermis-derived I-TAC triggers a sustained Th2-response that determines the outcome of a complex immunological process.