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Identification of IL-40, a Novel B Cell?Associated Cytokine #MMPMID28978694
J Immunol 2017[Nov]; 199 (9): 3326-35 PMID28978694show ga
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-?1, 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.
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J+Immunol 2017 ; 199 (9): 3326-35
