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IL-35 and Autoimmunity: a Comprehensive Perspective

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Abstract

Interleukin 35 (IL-35) is the most recently identified member of the IL-12 family of cytokines and offers the potential to be a target for new therapies for autoimmune, inflammatory, and infectious diseases. Similar to other members of the IL-12 family including IL-12, IL-23, and IL-27, IL-35 is composed of a heterodimer of α and β chains, which in the case of IL-35 are the p35 and Epstein–Barr virus-induced gene 3 (EBI3) proteins. However, unlike its proinflammatory relatives, IL-35 has immunosuppressive effects that are mediated through regulatory T and B cells. Although there are limited data available regarding the role of IL-35 in human autoimmunity, several murine models of autoimmunity suggest that IL-35 may have potent effects in regulating immunoreactivity via IL-10-dependent mechanisms. We suggest that similar effects are operational in human disease and IL-35-directed therapies hold significant promise. In particular, we emphasize that IL-35 has immunosuppressive ability that are mediated via regulatory T and B cells that are IL-10 dependent. Further, although deletion of IL-35 does not result in spontaneous breach of tolerance, recombinant IL-35 can improve autoimmune responses in several experimental models.

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Authors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, Davis, CA, 95616, USA

    Jinjung Choi, Patrick S. C. Leung & M. Eric Gershwin

  2. Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, 95817, USA

    Christopher Bowlus

  3. Division of Rheumatology, CHA University Medical Center, Bundang, 463-712, Korea

    Jinjung Choi

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  1. Jinjung Choi
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  2. Patrick S. C. Leung
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  4. M. Eric Gershwin
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Correspondence to M. Eric Gershwin.

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Choi, J., Leung, P.S.C., Bowlus, C. et al. IL-35 and Autoimmunity: a Comprehensive Perspective. Clinic Rev Allerg Immunol 49, 327–332 (2015). https://doi.org/10.1007/s12016-015-8468-9

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