Cellular FLIP long isoform transgenic mice overcome inherent Th2-biased immune responses to efficiently resolve Leishmania major infection.

c-FLIP(L) expression in T cells is required for mounting effective T cell responses and can also be critical for effector T cell differentiation, as has recently been shown by a number of in vivo studies in conditional knockout and transgenic mouse systems. Available data supports therefore a novel immunomodulatory role of this anti-apoptotic protein besides its traditionally proposed function in homeostatic maintenance of T cell populations. In this study, the responses to infection with Leishmania major of mice over-expressing FLIP(L) specifically in the T cell compartment (TgFLIP(L)) are assessed. Although previous studies have shown that FLIP(L) drives T cells towards a T(h)2 differentiation programme in various autoimmune and allergic paradigms, in this study, we show that TgFLIP(L) are able to overcome this T(h)2 bias in a dermal L. major infection model to mount a robust T(h)1 response to pathogen and effectively clear infection. Our results suggest that vaccination protocols designed to enhance FLIP(L) expression in T cells may be useful for the treatment of autoimmune diseases like multiple sclerosis, without necessarily compromising immune responses towards infectious agents.