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J Immunol. 2017 Nov 1;199(9):3326-3335. doi: 10.4049/jimmunol.1700534. Epub 2017 Oct 4.

Identification of IL-40, a Novel B Cell-Associated Cytokine.

Author information

1
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
2
Institute for Immunology, University of California, Irvine, Irvine, CA 92697.
3
Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697; and.
4
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697.
5
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697; azlotnik@uci.edu.

Abstract

We describe a novel B cell-associated cytokine, encoded by an uncharacterized gene (C17orf99; chromosome 17 open reading frame 99), that is expressed in bone marrow and fetal liver and whose expression is also induced in peripheral B cells upon activation. C17orf99 is only present in mammalian genomes, and it encodes a small (∼27-kDa) secreted protein unrelated to other cytokine families, suggesting a function in mammalian immune responses. Accordingly, C17orf99 expression is induced in the mammary gland upon the onset of lactation, and a C17orf99-/- mouse exhibits reduced levels of IgA in the serum, gut, feces, and lactating mammary gland. C17orf99-/- mice have smaller and fewer Peyer's patches and lower numbers of IgA-secreting cells. The microbiome of C17orf99-/- mice exhibits altered composition, likely a consequence of the reduced levels of IgA in the gut. Although naive B cells can express C17orf99 upon activation, their production increases following culture with various cytokines, including IL-4 and TGF-β1, suggesting that differentiation can result in the expansion of C17orf99-producing B cells during some immune responses. Taken together, these observations indicate that C17orf99 encodes a novel B cell-associated cytokine, which we have called IL-40, that plays an important role in humoral immune responses and may also play a role in B cell development. Importantly, IL-40 is also expressed by human activated B cells and by several human B cell lymphomas. The latter observations suggest that it may play a role in the pathogenesis of certain human diseases.

PMID:
28978694
PMCID:
PMC5667921
DOI:
10.4049/jimmunol.1700534
[Indexed for MEDLINE]
Free PMC Article

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