Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells

Timotheus Y.F. Halim; Batika M.J. Rana; Jennifer A. Walker; Bernhard Kerscher; Martin D. Knolle; Helen E. Jolin; Eva M. Serrao; Liora Haim-Vilmovsky; Sarah A. Teichmann; Hans-Reimer Rodewald; Marina Botto; Timothy J. Vyse; Padraic G. Fallon; Zhi Li; David R. Withers; Andrew N.J. McKenzie

doi:10.1016/j.immuni.2018.05.003

Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells

Timotheus Y.F. Halim, Batika M.J. Rana, Jennifer A. Walker, Bernhard Kerscher, Martin D. Knolle, Helen E. Jolin, Eva M. Serrao, Liora Haim-Vilmovsky, Sarah A. Teichmann, Hans-Reimer Rodewald, Marina Botto, Timothy J. Vyse, Padraic G. Fallon, Zhi Li, David R. Withers, Andrew N.J. McKenzie

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Abstract

The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7raCre/+Tnfsf4fl/fl mice). Moreover, Il7raCre/+Tnfsf4fl/fl mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish.

Original language	English
Journal	Immunity
Early online date	12 Jun 2018
DOIs	https://doi.org/10.1016/j.immuni.2018.05.003
Publication status	E-pub ahead of print - 12 Jun 2018

Keywords

ILC2
OX40L
type 2 immunity
Th2 cells
Treg cells
allergy
helminth
IL-33

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Tissue-Restricted Adaptive Type 2_HALIM_Accepted10May2018_GOLD VoR (CC BY)Final published version, 4.14 MBLicence: CC BY

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Halim, T. Y. F., Rana, B. M. J., Walker, J. A., Kerscher, B., Knolle, M. D., Jolin, H. E., Serrao, E. M., Haim-Vilmovsky, L., Teichmann, S. A., Rodewald, H.-R., Botto, M., Vyse, T. J., Fallon, P. G., Li, Z., Withers, D. R., & McKenzie, A. N. J. (2018). Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells. Immunity. Advance online publication. https://doi.org/10.1016/j.immuni.2018.05.003

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title = "Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells",

abstract = "The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7raCre/+Tnfsf4fl/fl mice). Moreover, Il7raCre/+Tnfsf4fl/fl mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish.",

keywords = "ILC2, OX40L, type 2 immunity, Th2 cells, Treg cells, allergy, helminth, IL-33",

author = "Halim, {Timotheus Y.F.} and Rana, {Batika M.J.} and Walker, {Jennifer A.} and Bernhard Kerscher and Knolle, {Martin D.} and Jolin, {Helen E.} and Serrao, {Eva M.} and Liora Haim-Vilmovsky and Teichmann, {Sarah A.} and Hans-Reimer Rodewald and Marina Botto and Vyse, {Timothy J.} and Fallon, {Padraic G.} and Zhi Li and Withers, {David R.} and McKenzie, {Andrew N.J.}",

year = "2018",

month = jun,

day = "12",

doi = "10.1016/j.immuni.2018.05.003",

language = "English",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

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Halim, TYF, Rana, BMJ, Walker, JA, Kerscher, B, Knolle, MD, Jolin, HE, Serrao, EM, Haim-Vilmovsky, L, Teichmann, SA, Rodewald, H-R, Botto, M, Vyse, TJ, Fallon, PG, Li, Z, Withers, DR & McKenzie, ANJ 2018, 'Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells', Immunity. https://doi.org/10.1016/j.immuni.2018.05.003

TY - JOUR

T1 - Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells

AU - Halim, Timotheus Y.F.

AU - Rana, Batika M.J.

AU - Walker, Jennifer A.

AU - Kerscher, Bernhard

AU - Knolle, Martin D.

AU - Jolin, Helen E.

AU - Serrao, Eva M.

AU - Haim-Vilmovsky, Liora

AU - Teichmann, Sarah A.

AU - Rodewald, Hans-Reimer

AU - Botto, Marina

AU - Vyse, Timothy J.

AU - Fallon, Padraic G.

AU - Li, Zhi

AU - Withers, David R.

AU - McKenzie, Andrew N.J.

PY - 2018/6/12

Y1 - 2018/6/12

N2 - The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7raCre/+Tnfsf4fl/fl mice). Moreover, Il7raCre/+Tnfsf4fl/fl mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish.

AB - The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7raCre/+Tnfsf4fl/fl mice). Moreover, Il7raCre/+Tnfsf4fl/fl mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish.

KW - ILC2

KW - OX40L

KW - type 2 immunity

KW - Th2 cells

KW - Treg cells

KW - allergy

KW - helminth

KW - IL-33

U2 - 10.1016/j.immuni.2018.05.003

DO - 10.1016/j.immuni.2018.05.003

M3 - Article

SN - 1074-7613

JO - Immunity

JF - Immunity

ER -

Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells

Abstract

Keywords

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