Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis

Liang Chi; Can Liu; Inta Gribonika; Julia Gschwend; Dan Corral; Seong Ji Han; Ai Ing Lim; Claudia A. Rivera; Verena M. Link; Alexandria C. Wells; Nicolas Bouladoux; Nicholas Collins; Djalma S. Lima-Junior; Michel Enamorado; Barbara Rehermann; Sophie Laffont; Jean Charles Guéry; Roxane Tussiwand; Christoph Schneider; Yasmine Belkaid

doi:10.1126/science.adk6200

Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis

Liang Chi, Can Liu, Inta Gribonika, Julia Gschwend, Dan Corral, Seong Ji Han, Ai Ing Lim, Claudia A. Rivera, Verena M. Link, Alexandria C. Wells, Nicolas Bouladoux, Nicholas Collins, Djalma S. Lima-Junior, Michel Enamorado, Barbara Rehermann, Sophie Laffont, Jean Charles Guéry, Roxane Tussiwand, Christoph Schneider, Yasmine Belkaid

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and activation in males, along with reduced tissue immunity. Collectively, our results reveal a role for the androgen-ILC2-dendritic cell axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.

Original language	English (US)
Journal	Science
Volume	384
Issue number	6692
DOIs	https://doi.org/10.1126/science.adk6200
State	Published - Apr 12 2024
Externally published	Yes

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Chi, L., Liu, C., Gribonika, I., Gschwend, J., Corral, D., Han, S. J., Lim, A. I., Rivera, C. A., Link, V. M., Wells, A. C., Bouladoux, N., Collins, N., Lima-Junior, D. S., Enamorado, M., Rehermann, B., Laffont, S., Guéry, J. C., Tussiwand, R., Schneider, C., & Belkaid, Y. (2024). Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis. Science, 384(6692). https://doi.org/10.1126/science.adk6200

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title = "Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis",

abstract = "Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and activation in males, along with reduced tissue immunity. Collectively, our results reveal a role for the androgen-ILC2-dendritic cell axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.",

author = "Liang Chi and Can Liu and Inta Gribonika and Julia Gschwend and Dan Corral and Han, {Seong Ji} and Lim, {Ai Ing} and Rivera, {Claudia A.} and Link, {Verena M.} and Wells, {Alexandria C.} and Nicolas Bouladoux and Nicholas Collins and Lima-Junior, {Djalma S.} and Michel Enamorado and Barbara Rehermann and Sophie Laffont and Gu{\'e}ry, {Jean Charles} and Roxane Tussiwand and Christoph Schneider and Yasmine Belkaid",

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day = "12",

doi = "10.1126/science.adk6200",

language = "English (US)",

volume = "384",

journal = "Science",

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Chi, L, Liu, C, Gribonika, I, Gschwend, J, Corral, D, Han, SJ, Lim, AI, Rivera, CA, Link, VM, Wells, AC, Bouladoux, N, Collins, N, Lima-Junior, DS, Enamorado, M, Rehermann, B, Laffont, S, Guéry, JC, Tussiwand, R, Schneider, C & Belkaid, Y 2024, 'Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis', Science, vol. 384, no. 6692. https://doi.org/10.1126/science.adk6200

TY - JOUR

T1 - Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis

AU - Chi, Liang

AU - Liu, Can

AU - Gribonika, Inta

AU - Gschwend, Julia

AU - Corral, Dan

AU - Han, Seong Ji

AU - Lim, Ai Ing

AU - Rivera, Claudia A.

AU - Link, Verena M.

AU - Wells, Alexandria C.

AU - Bouladoux, Nicolas

AU - Collins, Nicholas

AU - Lima-Junior, Djalma S.

AU - Enamorado, Michel

AU - Rehermann, Barbara

AU - Laffont, Sophie

AU - Guéry, Jean Charles

AU - Tussiwand, Roxane

AU - Schneider, Christoph

AU - Belkaid, Yasmine

PY - 2024/4/12

Y1 - 2024/4/12

N2 - Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and activation in males, along with reduced tissue immunity. Collectively, our results reveal a role for the androgen-ILC2-dendritic cell axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.

AB - Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and activation in males, along with reduced tissue immunity. Collectively, our results reveal a role for the androgen-ILC2-dendritic cell axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.

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VL - 384

JO - Science

JF - Science

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Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis

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