IL17B, a Novel Member of the IL17 Cytokine Family, Promotes Type 2 Inflammation

The IL17 family of cytokines are involved in host defense mechanisms against bacteria, fungi and other pathogens. While the IL17A, IL17F and IL17C family members induce overlapping inflammatory cascades that promote neutrophil mediated immunity, IL17E, or IL25, contributes to Type 2 immune responses and eosinophil activity.  Numerous genetic and pharmacological studies have demonstrated the importance of these cytokines in mucosal immune responses.  In contrast, little is known about the biology of the related family member, IL17B.  We now report that IL17B shares many functional properties with IL25, including induction of Type 2 cytokine responses in vivo and receptor usage. We demonstrate that akin to IL25, IL17B activity requires the IL17RA and IL17RB receptor subunits. These data are consistent with other reports describing IL17RA as a shared receptor subunit for this cytokine family, and the in vitro data demonstrating physical interaction between IL17RB and IL17B.  In cellular assays IL17B induces Type 2 cytokine expression, and can augments IL25 activities.  These data suggest that IL17B also participates in Type 2 inflammatory responses, poising this as another IL17 family member contributing to mucosal immune responses.  Our data shed light on the biological properties of this novel cytokine member.