title: Cytokine crowdsourcing: multicellular production of TH17-associated cytokines.
abstract: In the 2 decades since its discovery, IL-17A has become appreciated for mounting robust, protective responses against bacterial and fungal pathogens. When improperly regulated, however, IL-17A can play a profoundly pathogenic role in perpetuating inflammation and has been linked to a wide variety of debilitating diseases. IL-17A is often present in a composite milieu that includes cytokines produced by TH17 cells (i.e., IL-17F, IL-21, IL-22, and IL-26) or associated with other T cell lineages (e.g., IFN-γ). These combinatorial effects add mechanistic complexity and more importantly, contribute differentially to disease outcome. Whereas TH17 cells are among the best-understood cell types that secrete IL-17A, they are frequently neither the earliest nor dominant producers. Indeed, non-TH17 cell sources of IL-17A can dramatically alter the course and severity of inflammatory episodes. The dissection of the temporal regulation of TH17-associated cytokines and the resulting net signaling outcomes will be critical toward understanding the increasingly intricate role of IL-17A and TH17-associated cytokines in disease, informing our therapeutic decisions. Herein, we discuss important non-TH17 cell sources of IL-17A and other TH17-associated cytokines relevant to inflammatory events in mucosal tissues.
authors.affiliation: *Center for Immunology and Microbial Disease, Albany Medical Center, Albany, New York, USA; and Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kathleen O
authors.initials: KO
authors.lastname: Busman-Sahay
authors.affiliation: *Center for Immunology and Microbial Disease, Albany Medical Center, Albany, New York, USA; and Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Travis
authors.initials: T
authors.lastname: Walrath
authors.affiliation: *Center for Immunology and Microbial Disease, Albany Medical Center, Albany, New York, USA; and Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.affiliation: *Center for Immunology and Microbial Disease, Albany Medical Center, Albany, New York, USA; and Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany oconnow@mail.amc.edu.
authors.forename: William
authors.initials: W
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D018448:Models, Immunological; D058504:Th17 Cells / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020381:Interleukin-17
keywords: IL-17A; IL-17F; IL-17RA; IL-22; inflammation; mucosal