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.
Tseveleki
Vivian
V
Laboratory of Molecular Genetics, Hellenic Pasteur Institute, 127 Vasilissis Sophias Avenue, 115 21 Athens, Greece.
Tsagozis
Panagiotis
P
Koutsoni
Olga
O
Dotsika
Eleni
E
Probert
Lesley
L
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D007156:Immunologic Memory; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation
D000953:Antigens, Protozoan; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506387:Cflar protein, mouse; D016207:Cytokines; D020033:Protein Isoforms