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

• Published in: The Journal of immunology (1950) Vol. 199; no. 9; pp. 3326 - 3335
• Main Authors: Catalan-Dibene, Jovani, Vazquez, Monica I, Luu, Van Phi, Nuccio, Sean-Paul, Karimzadeh, Alborz, Kastenschmidt, Jenna M, Villalta, S Armando, Ushach, Irina, Pone, Egest J, Casali, Paolo, Raffatellu, Manuela, Burkhardt, Amanda M, Hernandez-Ruiz, Marcela, Heller, Gina, Hevezi, Peter A, Zlotnik, Albert
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 01.11.2017
• Subjects: Animals; B-cell lymphoma; B-Lymphocytes - immunology; Bone marrow; Cell activation; Cell culture; Chromosome 17; Cytokines; Fetuses; Gene Expression Regulation - immunology; Genomes; Humans; Immune response (humoral); Immunoglobulin A; Immunoglobulin A - immunology; Interleukin 4; Interleukins - genetics; Interleukins - immunology; Jurkat Cells; Lactation; Liver; Lymphocytes B; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - immunology; Mammary gland; Mice; Mice, Knockout; Microbiomes; Pathogenesis; Peyer's Patches - immunology; Production increases; Rodents; Transforming growth factor-b1
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1700534

We describe a novel B cell-associated cytokine, encoded by an uncharacterized gene ( ; 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. 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, expression is induced in the mammary gland upon the onset of lactation, and a mouse exhibits reduced levels of IgA in the serum, gut, feces, and lactating mammary gland. mice have smaller and fewer Peyer's patches and lower numbers of IgA-secreting cells. The microbiome of mice exhibits altered composition, likely a consequence of the reduced levels of IgA in the gut. Although naive B cells can express 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 -producing B cells during some immune responses. Taken together, these observations indicate that 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.