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A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity 期刊论文
NATURE, 2020, 577 (7790) : 416-+
作者:  Morley, Jessica;  Cowls, Josh;  Taddeo, Mariarosaria;  Floridi, Luciano
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

Humoral immune responses to immunization and infection and susceptibilities to antibody-mediated autoimmunity are generally lower in males(1-3). However, the mechanisms underlying such sexual dimorphism are not well understood. Here we show that there are intrinsic differences between the B cells that produce germinal centres in male and female mice. We find that antigen-activated male B cells do not position themselves as efficiently as female B cells in the centre of follicles in secondary lymphoid organs, in which germinal centres normally develop. Moreover, GPR174-an X-chromosome-encoded G-protein-coupled receptor-suppresses the formation of germinal centres in male, but not female, mice. This effect is intrinsic to B cells, and correlates with the GPR174-enhanced positioning of B cells towards the T-cell-B-cell border of follicles, and the distraction of male, but not female, B cells from S1PR2-driven follicle-centre localization. Biochemical fractionation of conditioned media that induce B-cell migration in a GPR174-dependent manner identifies CCL21 as a GPR174 ligand. In response to CCL21, GPR174 triggers a calcium flux and preferentially induces the migration of male B cells  GPR174 also becomes associated with more G alpha i protein in male than in female B cells. Male B cells from orchidectomized mice exhibit impaired GPR174-mediated migration to CCL21, and testosterone treatment rescues this defect. Female B cells from testosterone-treated mice exhibit male-like GPR174-G alpha i association and GPR174-mediated migration. Deleting GPR174 from male B cells causes more efficient positioning towards the follicular centre, the formation of more germinal centres and an increased susceptibility to B-cell-dependent experimental autoimmune encephalomyelitis. By identifying GPR174 as a receptor for CCL21 and demonstrating its sex-dependent control of B-cell positioning and participation in germinal centres, we have revealed a mechanism by which B-cell physiology is fine-tuned to impart sexual dimorphism to humoral immunity.


  
Sex-specific adipose tissue imprinting of regulatory T cells 期刊论文
NATURE, 2020, 579 (7800) : 581-+
作者:  Qureshi, Abdul Aziz;  Suades, Albert;  Matsuoka, Rei;  Brock, Joseph;  McComas, Sarah E.;  Nji, Emmanuel;  Orellana, Laura;  Claesson, Magnus;  Delemotte, Lucie;  Drew, David
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

Adipose tissue is an energy store and a dynamic endocrine organ(1,2). In particular, visceral adipose tissue (VAT) is critical for the regulation of systemic metabolism(3,4). Impaired VAT function-for example, in obesity-is associated with insulin resistance and type 2 diabetes(5,6). Regulatory T (T-reg) cells that express the transcription factor FOXP3 are critical for limiting immune responses and suppressing tissue inflammation, including in the VAT(7-9). Here we uncover pronounced sexual dimorphism in T-reg cells in the VAT. Male VAT was enriched for T-reg cells compared with female VAT, and T-reg cells from male VAT were markedly different from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. Heightened inflammation in the male VAT facilitated the recruitment of T-reg cells via the CCL2-CCR2 axis. Androgen regulated the differentiation of a unique IL-33-producing stromal cell population specific to the male VAT, which paralleled the local expansion of T-reg cells. Sex hormones also regulated VAT inflammation, which shaped the transcriptional landscape of VAT-resident T-reg cells in a BLIMP1 transcription factor-dependent manner. Overall, we find that sex-specific differences in T-reg cells from VAT are determined by the tissue niche in a sex-hormone-dependent manner to limit adipose tissue inflammation.


Visceral adipose tissue contains populations of regulatory T cells that exhibit sexual dimorphism, determined by the surrounding niche, and differ between male and female mice in terms of cell number, phenotype, transcriptional landscape and chromatin accessibility.


  
Low siring success of females with an acquired male function illustrates the legacy of sexual dimorphism in constraining the breakdown of dioecy 期刊论文
ECOLOGY LETTERS, 2019, 22 (3) : 486-497
作者:  del Blanco, Luis Santos;  Tudor, Eleri;  Pannell, John R.
收藏  |  浏览/下载:5/0  |  提交时间:2019/04/09
Dioecy  functional hermaphroditism  gain curves  inflorescence architecture  Mercurialis annua  monoecy  sex allocation  sexual dimorphism  
Sexual dimorphism in immunity across animals: a meta-analysis 期刊论文
ECOLOGY LETTERS, 2018, 21 (12) : 1885-1894
作者:  Kelly, Clint D.;  Stoehr, Andrew M.;  Nunn, Charles;  Smyth, Kendra N.;  Prokop, Zofia M.
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09
Immune response  immunity  life-history  sexual dimorphism  
Sex differences in adult mortality rate mediated by early-life environmental conditions 期刊论文
ECOLOGY LETTERS, 2018, 21 (2) : 235-242
作者:  Griffin, Robert M.;  Hayward, Adam D.;  Bolund, Elisabeth;  Maklakov, Alexei A.;  Lummaa, Virpi
收藏  |  浏览/下载:3/0  |  提交时间:2019/04/09
Development  environmental variation  humans  life-history  sexual dimorphism  
Parabolic variation in sexual selection intensity across the range of a cold-water pipefish: implications for susceptibility to climate change 期刊论文
GLOBAL CHANGE BIOLOGY, 2017, 23 (9)
作者:  Monteiro, Nuno;  Cunha, Mario;  Ferreira, Lidia;  Vieira, Natividade;  Antunes, Agostinho;  Lyons, David;  Jones, Adam G.
收藏  |  浏览/下载:2/0  |  提交时间:2019/04/09
Bergmann'  s rule  coloration  dimorphism  distribution  expansion  investment  Nerophis lumbriciformis  Rensch'  s rule  secondary sexual characters  Syngnathidae