Protein IL-40
extracellular space
Identification of IL-40, a Novel B Cell-Associated Cytokine.
We describe a novel B cell-associated cytokine, encoded by an uncharacterized gene (<i>C17orf99</i>; 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. <i>C17orf99</i> 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, <i>C17orf99</i> expression is induced in the mammary gland upon the onset of lactation, and a <i>C17orf99</i><sup>-/-</sup> mouse exhibits reduced levels of IgA in the serum, gut, feces, and lactating mammary gland. <i>C17orf99</i><sup>-/-</sup> mice have smaller and fewer Peyer's patches and lower numbers of IgA-secreting cells. The microbiome of <i>C17orf99<sup>-/-</sup></i> mice exhibits altered composition, likely a consequence of the reduced levels of IgA in the gut. Although naive B cells can express <i>C17orf99</i> 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 <i>C17orf99</i>-producing B cells during some immune responses. Taken together, these observations indicate that <i>C17orf99</i> 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.