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 αand βsubunits pairing may exist in nature and may constitute a new class of therapeutic cytokines.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000262-18
Application #
8737609
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2013
Total Cost
$260,031
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Wang, Ren-Xi; Yu, Cheng-Rong; Dambuza, Ivy M et al. (2014) Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med 20:633-41
Egwuagu, Charles E (2009) STAT3 in CD4+ T helper cell differentiation and inflammatory diseases. Cytokine 47:149-56