Regulation of cytokine secretion in human CD127(+) LTi-like innate lymphoid cells by Toll-like receptor 2.
Lymphoid tissue inducer cells are members of an emerging family of innate lymphoid cells (ILC). Although these cells were originally reported to produce cytokines such as interleukin-17 (IL-17) and IL-22, we demonstrate here that human CD127(+)RORC(+) and CD56(+)CD127(+) LTi-like ILC also express IL-2, IL-5, and IL-13 after activation with physiologic stimuli such as common γ-chain cytokines, Toll-like receptor (TLR) 2 ligands, or IL-23. Whereas TLR2 signaling induced IL-5, IL-13, and IL-22 expression in a nuclear factor κB (NF-κB)-dependent manner, IL-23 costimulation induced only IL-22 production. CD127(+) LTi-like ILC displayed clonal heterogeneity for IL-13 and IL-5 production, suggesting in vivo polarization. Finally, we identified a role for autocrine IL-2 signaling in mediating the effects of TLR2 stimulation on CD56(+)CD127(+) and CD127(+) LTi-like ILC. These results indicate that human LTi-like ILC can directly sense bacterial components and unravel a previously unrecognized functional heterogeneity among this important population of innate lymphoid cells.
Department of Immunology, Genentech, South San Francisco, CA 94080, USA.
Natasha K
NK
Crellin
Sara
S
Trifari
Charles D
CD
Kaplan
Naoko
N
Satoh-Takayama
James P
JP
Di Santo
Hergen
H
Spits
D000818:Animals; D019898:Autocrine Communication / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D014066:Palatine Tonsil / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
D016207:Cytokines; D053699:Interleukin-7 Receptor alpha Subunit; D016328:NF-kappa B; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2