Identification of IL-40, a novel B cell-associated cytokine

Jovani Catalan-Dibene, Monica I. Vazquez, Van Phi Luu, Sean Paul Nuccio, Alborz Karimzadeh, Jenna M. Kastenschmidt, S. Armando Villalta, Irina Ushach, Egest J. Pone, Paolo Casali, Manuela Raffatellu, Amanda M. Burkhardt, Marcela Hernandez-Ruiz, Gina Heller, Peter A. Hevezi, Albert Zlotnik

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)3326-3335
Number of pages10
JournalJournal of Immunology
Volume199
Issue number9
DOIs
StatePublished - Nov 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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