TY - JOUR
T1 - Antigen-presenting ILC3 regulate T cell-dependent IgA responses to colonic mucosal bacteria
AU - Melo-Gonzalez, Felipe
AU - Kammoun, Hana
AU - Evren, Elza
AU - Dutton, Emma E.
AU - Papadopoulou, Markella
AU - Bradford, Barry M.
AU - Tanes, Ceylan
AU - Fardus-Reid, Fahmina
AU - Swann, Jonathan R.
AU - Bittinger, Kyle
AU - Mabbott, Neil A.
AU - Vallance, Bruce A.
AU - Willinger, Tim
AU - Withers, David R.
AU - Hepworth, Matthew R.
N1 - Publisher Copyright:
© 2019 Melo-Gonzalez et al.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Intestinal immune homeostasis is dependent upon tightly regulated and dynamic host interactions with the commensal microbiota. Immunoglobulin A (IgA) produced by mucosal B cells dictates the composition of commensal bacteria residing within the intestine. While emerging evidence suggests the majority of IgA is produced innately and may be polyreactive, mucosal-dwelling species can also elicit IgA via T cell-dependent mechanisms. However, the mechanisms that modulate the magnitude and quality of T cell-dependent IgA responses remain incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3) regulate steady state interactions between T follicular helper cells (TfH) and B cells to limit mucosal IgA responses. ILC3 used conserved migratory cues to establish residence within the interfollicular regions of the intestinal draining lymph nodes, where they act to limit TfH responses and B cell class switching through antigen presentation. The absence of ILC3-intrinsic antigen presentation resulted in increased and selective IgA coating of bacteria residing within the colonic mucosa. Together these findings implicate lymph node resident, antigen-presenting ILC3 as a critical regulatory checkpoint in the generation of T cell-dependent colonic IgA and suggest ILC3 act to maintain tissue homeostasis and mutualism with the mucosal-dwelling commensal microbiota.
AB - Intestinal immune homeostasis is dependent upon tightly regulated and dynamic host interactions with the commensal microbiota. Immunoglobulin A (IgA) produced by mucosal B cells dictates the composition of commensal bacteria residing within the intestine. While emerging evidence suggests the majority of IgA is produced innately and may be polyreactive, mucosal-dwelling species can also elicit IgA via T cell-dependent mechanisms. However, the mechanisms that modulate the magnitude and quality of T cell-dependent IgA responses remain incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3) regulate steady state interactions between T follicular helper cells (TfH) and B cells to limit mucosal IgA responses. ILC3 used conserved migratory cues to establish residence within the interfollicular regions of the intestinal draining lymph nodes, where they act to limit TfH responses and B cell class switching through antigen presentation. The absence of ILC3-intrinsic antigen presentation resulted in increased and selective IgA coating of bacteria residing within the colonic mucosa. Together these findings implicate lymph node resident, antigen-presenting ILC3 as a critical regulatory checkpoint in the generation of T cell-dependent colonic IgA and suggest ILC3 act to maintain tissue homeostasis and mutualism with the mucosal-dwelling commensal microbiota.
UR - http://www.scopus.com/inward/record.url?scp=85064198442&partnerID=8YFLogxK
U2 - 10.1084/jem.20180871
DO - 10.1084/jem.20180871
M3 - Article
C2 - 30814299
AN - SCOPUS:85064198442
SN - 0022-1007
VL - 216
SP - 728
EP - 742
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -