Role of IL-12 family cytokines in human autoimmune Uveitis

National Eye Institute

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Abstract

IL-12 family cytokines are important in host immunity. Some members (IL-12, IL-23) play crucial roles in pathogenesis of organ-specific autoimmune diseases by inducing the differentiation of Th1 and Th17 lymphocytes, while others (IL-27 and IL-35) suppress inflammatory responses and limit tissue injury induced by these T cell subsets. In this study, we have genetically engineered: (i) Recombinant heterodimeric IL-35 (human & mouse); (i) Recombinant heterodimeric IL-27 (human & mouse); Novel recombinant IL27p28/IL12p40 heterodimeric cytokine (p28/p40); (i) Recombinant single chain mouse IL12p35; (i) Recombinant single chain mouse IL12p40; (i) Recombinant single chain mouse IL27p28; (i) Recombinant single chain mouse Ebi3; We investigated whether each of these recombinant heterodimeric or single chain cytokines can be used to treat uveitis, a CNS inflammatory disease. Thus, far we have shown that IL-35, IL-27 and IL27p28/IL12p40 are effective in ameliorating EAU while p35, Ebi3 were found to inhibit lymphocyte proliferation. Taken together these important proof-of-concept studies, suggest that cytokines comprising of unique IL-12 α and β subunits pairing may exist in nature and may constitute a new class of therapeutic cytokines.