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

Chi, Liang ; Liu, Can ; Gribonika, Inta LU orcid ; Gschwend, Julia ; Corral, Dan ; Han, Seong-Ji ; Lim, Ai Ing ; Rivera, Claudia A ; Link, Verena M and Wells, Alexandria C , et al. (2024) In Science (New York, N.Y.) 384(6692).
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,... (More)

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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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Female, Male, Androgens/metabolism, Dendritic Cells/immunology, Gonadal Steroid Hormones/metabolism, Immunity, Innate, Lymphocytes/immunology, Sex Characteristics, Skin/immunology, Animals, Mice, Mice, Inbred C57BL, Microbiota
in
Science (New York, N.Y.)
volume
384
issue
6692
article number
eadk6200
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85190563347
  • pmid:38574174
ISSN
1095-9203
DOI
10.1126/science.adk6200
language
English
LU publication?
no
id
8794aa11-2c83-4106-8f85-79f5d7f776fd
date added to LUP
2025-12-20 13:21:34
date last changed
2025-12-22 14:47:14
@article{8794aa11-2c83-4106-8f85-79f5d7f776fd,
  abstract     = {{<p>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.</p>}},
  author       = {{Chi, Liang and Liu, Can and Gribonika, Inta and Gschwend, Julia and Corral, Dan and Han, Seong-Ji and Lim, Ai Ing and Rivera, Claudia A and Link, Verena M and Wells, Alexandria C and Bouladoux, Nicolas and Collins, Nicholas and Lima-Junior, Djalma S and Enamorado, Michel and Rehermann, Barbara and Laffont, Sophie and Guéry, Jean-Charles and Tussiwand, Roxane and Schneider, Christoph and Belkaid, Yasmine}},
  issn         = {{1095-9203}},
  keywords     = {{Female; Male; Androgens/metabolism; Dendritic Cells/immunology; Gonadal Steroid Hormones/metabolism; Immunity, Innate; Lymphocytes/immunology; Sex Characteristics; Skin/immunology; Animals; Mice; Mice, Inbred C57BL; Microbiota}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{6692}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science (New York, N.Y.)}},
  title        = {{Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis}},
  url          = {{http://dx.doi.org/10.1126/science.adk6200}},
  doi          = {{10.1126/science.adk6200}},
  volume       = {{384}},
  year         = {{2024}},
}