TY - JOUR
T1 - Cytokine crowdsourcing
T2 - Multicellular production of TH17-associated cytokines
AU - Busman-Sahay, Kathleen O.
AU - Walrath, Travis
AU - Huber, Samuel
AU - O’Connor, William
N1 - Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - IL-17A
KW - IL-17F
KW - IL-17RA
KW - IL-22
KW - Inflammation
KW - Mucosal
UR - http://www.scopus.com/inward/record.url?scp=84928756956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928756956&partnerID=8YFLogxK
U2 - 10.1189/jlb.3RU0814-386R
DO - 10.1189/jlb.3RU0814-386R
M3 - Review article
C2 - 25548251
AN - SCOPUS:84928756956
SN - 0741-5400
VL - 97
SP - 499
EP - 509
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -