Interleukin (IL)-35 is raising our expectations

Abstract

PURPOSE To elucidate and discuss the role of IL-35 in immunity to parasitic and bacterial infections as well as in autoimmunity in terms of its anti-inflammatory properties, we highlight significant findings on this novel member of the IL-12 family. METHODS Studies using genetically deficient mice have greatly enhanced our understanding of the biology of IL-35. On the basis of data derived from the analysis of these genetically deficient mice published by NIH, we focus on the key features of this heterodimeric cytokine, especially its relation to the other IL-12 family members, and discuss its potential relevance to the clinical usage. PRINCIPAL FINDINGS IL-35 is required for the CD4+CD25+ Treg cells-mediated immune regulation, the alleviation of some inflammatory responses, as well as the expansion of CD4+CD25- Teff cells simultaneously. Moreover, administration or augmentation of IL-35 suppresses some diseases of autoimmune or allergic origin like collagen-induced arthritis or Helicobacter-induced colitis in animal models, demonstrating its potential in therapy of diseases mediated by inflammatory cytokines. However, some questions involving it are still unclear, including the composition of IL-35 receptor, IL-35-related cell signaling pathway, the different expression patterns of IL-35 between human and murine T cells, etc. CONCLUSION As our understanding of the IL-35 is rapidly growing and changing, it will bring us more therapeutic strategies towards some intractable immune diseases such as Lupus Erythematosus.