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

Immunology and Immunotherapy

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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 (Il7ra^Cre/+Tnfsf4^fl/fl mice). Moreover, Il7ra^Cre/+Tnfsf4^fl/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
Pages (from-to)	1195-1207.e6
Number of pages	20
Journal	Immunity
Volume	48
Issue number	6
Early online date	12 Jun 2018
DOIs	https://doi.org/10.1016/j.immuni.2018.05.003
Publication status	Published - 19 Jun 2018

Keywords

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

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Timotheus_Halim_et_al_Tissue-restricted_adaptive_type_2_immunity_Immunity_2018
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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, 48(6), 1195-1207.e6. 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,

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

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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, vol. 48, no. 6, pp. 1195-1207.e6. https://doi.org/10.1016/j.immuni.2018.05.003

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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 - 2018/6/19

Y1 - 2018/6/19

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

C2 - 29907525

SN - 1074-7613

VL - 48

SP - 1195-1207.e6

JO - Immunity

JF - Immunity

IS - 6

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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