TNF superfamily member TL1A elicits type 2 innate lymphoid cells at mucosal barriers.
Immune responses at mucosal barriers are regulated by innate type 2 lymphoid cells (ILC2s) that elaborate effector cytokines interleukins 5 and 13 (IL5 and IL13). IL25 and IL33 are key cytokines that support ILC2s; however, mice deficient in these pathways retain some functional ILC2s. Analysis of human and murine cells revealed that ILC2s highly express tumor necrosis factor (TNF)-receptor superfamily member DR3 (TNFRSF25). Engagement of DR3 with cognate ligand TL1A promoted ILC2 expansion, survival, and function. Exogenous protein or genetic overexpression of TL1A activated ILC2s independent of IL25 or IL33. Dr3(-/-) mice failed to control gut helminthic infections, and failed to mount ILC2 responses in the lung after nasal challenge with papain. Our data demonstrate a key role for TL1A in promoting ILC2s at mucosal barriers.
Department of Immunology, Genentech, South San Francisco, California, USA.
X
X
Yu
Department of Immunology, Genentech, South San Francisco, California, USA.
R
R
Pappu
Department of Immunology, Genentech, South San Francisco, California, USA.
V
V
Ramirez-Carrozzi
Department of Immunology, Genentech, South San Francisco, California, USA.
N
N
Ota
Department of Pathology, Genentech, South San Francisco, California, USA.
P
P
Caplazi
Department of Translational Immunology, Genentech, South San Francisco, California, USA.
J
J
Zhang
Department of Translational Immunology, Genentech, South San Francisco, California, USA.
D
D
Yan
Department of Translational Immunology, Genentech, South San Francisco, California, USA.
M
M
Xu
Department of Translational Immunology, Genentech, South San Francisco, California, USA.
W P
WP
Lee
Department of Immunology, Genentech, South San Francisco, California, USA.
J L
JL
Grogan
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D009559:Nippostrongylus / Q000276:immunology; D010206:Papain / Q000276:immunology; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics* / Q000378:metabolism
D020381:Interleukin-17; D053219:Receptors, Tumor Necrosis Factor, Member 25; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D010206:Papain