The IL-12 family cytokines have emerged as an important group of cytokines that regulate many critical aspects of host immunity, including antigen presentation, T cell lineage commitment and cytokine signaling. IL-12 family cytokines are comprised of heterodimeric protein subunits. Unique combinations of subunits can form through covalent and non-covalent binding and these include IL-12 (IL12p40 &IL12p35), IL-23 (IL12p40 and IL23p19), IL-27 (IL27p28 &EBI3 and a novel pairing between IL12p35 and EBI3 now constitutes the newly described member, IL-35. Individual subunits (e.g. IL27p28) have also been shown to have intrinsic biological activities. Our research goal has been to generate various combinations of IL-12 cytokine family subunit chains as basis for a new class of therapeutic cytokines. In this regard we have genetically engineered novel IL-12-like cytokines by pairing IL12p40 to IL27p28 and EBI3 to IL23p19 and are now defining their potential biological activities on lymphocytes and ocular cells. Specifically, we intend to use these reagents to test each subunit and various subunit combination in T cell assays to determine if they exhibit any useful biological activities and eventually, to explore their use in treating ocular diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000350-14
Application #
8737621
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2013
Total Cost
$354,588
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Yu, Cheng-Rong; Hayashi, Kozaburo; Lee, Yun Sang et al. (2015) Suppressor of cytokine signaling 1 (SOCS1) mitigates anterior uveitis and confers protection against ocular HSV-1 infection. Inflammation 38:555-65
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