Interleukin-35 administration counteracts established murine type 1 diabetes – possible involvement of regulatory T cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-10

AUTHORS

Kailash Singh, Erik Kadesjö, Julia Lindroos, Marcus Hjort, Marcus Lundberg, Daniel Espes, Per-Ola Carlsson, Stellan Sandler, Lina Thorvaldson

ABSTRACT

The anti-inflammatory cytokine IL-35 is produced by regulatory T (Treg) cells to suppress autoimmune and inflammatory responses. The role of IL-35 in type 1 diabetes (T1D) remains to be answered. To elucidate this, we investigated the kinetics of Treg cell response in the multiple low dose streptozotocin induced (MLDSTZ) T1D model and measured the levels of IL-35 in human T1D patients. We found that Treg cells were increased in MLDSTZ mice. However, the Treg cells showed a decreased production of anti-inflammatory (IL-10, IL-35, TGF-β) and increased pro-inflammatory (IFN-γ, IL-2, IL-17) cytokines, indicating a phenotypic shift of Treg cells under T1D condition. IL-35 administration effectively both prevented development of, and counteracted established MLDSTZ T1D, seemingly by induction of Eos expression and IL-35 production in Treg cells, thus reversing the phenotypic shift of the Treg cells. IL-35 administration reversed established hyperglycemia in NOD mouse model of T1D. Moreover, circulating IL-35 levels were decreased in human T1D patients compared to healthy controls. These findings suggest that insufficient IL-35 levels play a pivotal role in the development of T1D and that treatment with IL-35 should be investigated in treatment of T1D and other autoimmune diseases. More... »

PAGES

12633

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/srep12633

    DOI

    http://dx.doi.org/10.1038/srep12633

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1007979630

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26224624


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