TY - JOUR
T1 - Identification of IL-40, a novel B cell-associated cytokine
AU - Catalan-Dibene, Jovani
AU - Vazquez, Monica I.
AU - Luu, Van Phi
AU - Nuccio, Sean Paul
AU - Karimzadeh, Alborz
AU - Kastenschmidt, Jenna M.
AU - Villalta, S. Armando
AU - Ushach, Irina
AU - Pone, Egest J.
AU - Casali, Paolo
AU - Raffatellu, Manuela
AU - Burkhardt, Amanda M.
AU - Hernandez-Ruiz, Marcela
AU - Heller, Gina
AU - Hevezi, Peter A.
AU - Zlotnik, Albert
N1 - Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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 C17orf992/2 mouse exhibits reduced levels of IgA in the serum, gut, feces, and lactating mammary gland. C17orf992/2 mice have smaller and fewer Peyer's patches and lower numbers of IgA-secreting cells. The microbiome of C17orf992/2 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-b1, 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.
AB - 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 C17orf992/2 mouse exhibits reduced levels of IgA in the serum, gut, feces, and lactating mammary gland. C17orf992/2 mice have smaller and fewer Peyer's patches and lower numbers of IgA-secreting cells. The microbiome of C17orf992/2 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-b1, 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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U2 - 10.4049/jimmunol.1700534
DO - 10.4049/jimmunol.1700534
M3 - Article
C2 - 28978694
AN - SCOPUS:85032032784
SN - 0022-1767
VL - 199
SP - 3326
EP - 3335
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -