{"title":"CCR8 + decidual regulatory T cells maintain maternal-fetal immune tolerance during early pregnancy","authors":"Zhuqing Li, Pinxin Si, Tingting Meng, Xiaoran Zhao, Chendi Zhu, Dunfang Zhang, Shutong Meng, Nianyu Li, Ran Liu, Tianxiang Ni, Junhao Yan, Hongchang Li, Ning Zhao, Chao Zhong, Yingying Qin, WanJun Chen, Zi-Jiang Chen, Xue Jiao","doi":"10.1126/sciimmunol.ado2463","DOIUrl":"https://doi.org/10.1126/sciimmunol.ado2463","url":null,"abstract":"Regulatory T (T <jats:sub>reg</jats:sub> ) cells play a vital role in maintaining maternal immune tolerance to the semiallogeneic fetus during pregnancy. T <jats:sub>reg</jats:sub> cell population heterogeneity and tissue-specific functions in the human decidua remain largely unknown. Here, using single-cell transcriptomic and T cell receptor sequencing of human CD4 <jats:sup>+</jats:sup> T cells from first-trimester deciduae and matched peripheral blood of pregnant women, we identified a highly activated, immunosuppressive CCR8 <jats:sup>+</jats:sup> T <jats:sub>reg</jats:sub> cell subset specifically enriched in the decidua (dT <jats:sub>reg</jats:sub> cells). CCR8 <jats:sup>+</jats:sup> dT <jats:sub>reg</jats:sub> cells were decreased in patients with recurrent pregnancy loss (RPL) and an abortion-prone mouse model. Depletion of CCR8 <jats:sup>+</jats:sup> dT <jats:sub>reg</jats:sub> cells increased susceptibility to fetal loss, with altered decidual immune profiles. Adoptive transfer of CCR8 <jats:sup>+</jats:sup> T <jats:sub>reg</jats:sub> cells rescued fetal loss in abortion-prone mice. The CCR8 ligand CCL1 was mainly produced by decidual CD49a <jats:sup>+</jats:sup> natural killer cells and was significantly decreased in patients with RPL. Our data demonstrate that CCR8 <jats:sup>+</jats:sup> dT <jats:sub>reg</jats:sub> cells are required to maintain maternal-fetal tolerance and highlight potential avenues for RPL therapies.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"44 1","pages":""},"PeriodicalIF":24.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wen Peng, Domien Vanneste, David Bejarano, Joan Abinet, Margot Meunier, Coraline Radermecker, Fabienne Perin, Didier Cataldo, Fabrice Bureau, Andreas Schlitzer, Qiang Bai, Thomas Marichal
{"title":"Endothelial-driven TGFβ signaling supports lung interstitial macrophage development from monocytes","authors":"Wen Peng, Domien Vanneste, David Bejarano, Joan Abinet, Margot Meunier, Coraline Radermecker, Fabienne Perin, Didier Cataldo, Fabrice Bureau, Andreas Schlitzer, Qiang Bai, Thomas Marichal","doi":"10.1126/sciimmunol.adr4977","DOIUrl":"https://doi.org/10.1126/sciimmunol.adr4977","url":null,"abstract":"Lung interstitial macrophages (IMs) are monocyte-derived parenchymal macrophages whose tissue-supportive functions remain unclear. Despite progress in understanding lung IM diversity and transcriptional regulation, the signals driving their development from monocytes and their functional specification remain unknown. Here, we found that lung endothelial cell–derived Tgfβ1 triggered a core Tgfβ receptor–dependent IM signature in mouse bone marrow–derived monocytes. Myeloid-specific impairment of Tgfβ receptor signaling severely disrupted monocyte-to-IM development, leading to the accumulation of perivascular immature monocytes, reduced IM numbers, and a loss of IM-intrinsic identity, a phenomenon similarly observed in the absence of endothelial-specific Tgfβ1. Mice lacking the Tgfβ receptor in monocytes and IMs exhibited altered monocyte and IM niche occupancy and hallmarks of aging including impaired immunoregulation, hyperinflation, and fibrosis. Our work identifies a Tgfβ signaling–dependent endothelial-IM axis that shapes IM development and sustains lung integrity, providing foundations for IM-targeted interventions in aging and chronic inflammation.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"108 1","pages":""},"PeriodicalIF":24.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum for the Research Article “Anti–immune complex antibodies are elicited during repeated immunization with HIV Env immunogens” by S. Brown et al.","authors":"","doi":"10.1126/sciimmunol.adx6798","DOIUrl":"10.1126/sciimmunol.adx6798","url":null,"abstract":"","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 106","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul Hsu, Eunice J. Choi, William H. Wong, Yun Hsuan Lin, Sara A. Vandenburgh, Yi Chia Liu, Priscilla Yao, Cynthia S. Indralingam, Gene W. Yeo, Elina I. Zuniga, Ananda W. Goldrath, Wei Wang, John T. Chang
{"title":"Foxo1 regulates intestinal tissue–resident memory CD8 T cell biology in an anatomic compartment– and context-specific manner","authors":"Paul Hsu, Eunice J. Choi, William H. Wong, Yun Hsuan Lin, Sara A. Vandenburgh, Yi Chia Liu, Priscilla Yao, Cynthia S. Indralingam, Gene W. Yeo, Elina I. Zuniga, Ananda W. Goldrath, Wei Wang, John T. Chang","doi":"10.1126/sciimmunol.adn1894","DOIUrl":"10.1126/sciimmunol.adn1894","url":null,"abstract":"<div >Tissue-resident memory CD8 T (T<sub>RM</sub>) cells serve as a front-line defense against microbial pathogens in barrier and mucosal tissues. Accurately predicting the roles of tissue-specific transcription factors (TFs) that regulate T<sub>RM</sub> biology remains a challenge. Here, by applying integrated transcriptomic and epigenomic analyses, we have identified an unexpected role for forkhead box O1 (Foxo1), a TF previously known to regulate circulating memory T cells, in intestinal T<sub>RM</sub> biology. Foxo1 repressed the maintenance of early small intestinal intraepithelial T<sub>RM</sub> cells in contrast with its actions in sustaining T<sub>RM</sub> cells from small intestinal lamina propria and colon and contrary to its broader role in promoting intestinal T<sub>RM</sub> cell formation. These findings highlight the emerging concept that the transcriptional regulation of T<sub>RM</sub> cells may be more complex and nuanced than previously appreciated and underscore the utility of integrated transcriptomic and epigenomic analyses in reconstructing TF-regulatory networks.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 106","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bcl11a maintains hematopoietic stem cell function but accelerates inflammation-driven exhaustion during aging","authors":"Jing Wang, Linlin Zhang, Xinyu Cui, Xiang Xu, Rui Guo, Kairui Li, Li Zhang, Bing Xu, Cizhong Jiang, Yong Yu","doi":"10.1126/sciimmunol.adr2041","DOIUrl":"10.1126/sciimmunol.adr2041","url":null,"abstract":"<div >Preserving hematopoietic stem cell (HSC) functionality is essential for maintaining healthy blood and the immune system throughout life. HSC function declines with age; however, the underlying mechanisms are not fully understood. Using an inducible mosaic mouse model to overexpress the transcription factor Bcl11a in the hematopoietic compartment, we found that an aging-related increase in Bcl11a mitigated HSC functional decline, promoted IL-1β production in the bone marrow (BM), and accelerated HSC attrition in a non–cell-autonomous manner. Aging-related inflammation in the BM enhanced Bcl11a and Fc receptor (FcR) expression in HSCs, and FcR signaling induced HSC differentiation. This was counteracted by Bcl11a through repression of <i>Fcer1g</i>. Bcl11a up-regulation promoted IL-1β production in BM myeloid cells, driving inflammation and HSC deterioration. Deletion of <i>Fcer1g</i>, or blocking IL-1β signaling, eliminated this non–cell-autonomous effect on HSC decline. These findings demonstrate that Bcl11a plays a dual role in HSCs during aging not only by cell-intrinsically preserving HSC function but also by promoting BM inflammation and HSC dysfunction.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 106","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hung Chan, Fengwu Li, Tatsuya Dokoshi, Kellen J. Cavagnero, Qing Li, Yang Chen, Carlos Aguilera, Teruaki Nakatsuji, Edward Liu, Aaryan Indra, Daping Yang, Ottaviani Valentina, Tomofumi Numata, Brittany Crown, Henry Li, Kevin J. Williams, Isaac M. Chiu, Steven J. Bensinger, WanJun Chen, Richard L. Gallo
{"title":"Psychological stress increases skin infection through the action of TGFβ to suppress immune-acting fibroblasts","authors":"Hung Chan, Fengwu Li, Tatsuya Dokoshi, Kellen J. Cavagnero, Qing Li, Yang Chen, Carlos Aguilera, Teruaki Nakatsuji, Edward Liu, Aaryan Indra, Daping Yang, Ottaviani Valentina, Tomofumi Numata, Brittany Crown, Henry Li, Kevin J. Williams, Isaac M. Chiu, Steven J. Bensinger, WanJun Chen, Richard L. Gallo","doi":"10.1126/sciimmunol.ads0519","DOIUrl":"10.1126/sciimmunol.ads0519","url":null,"abstract":"<div >Infections after psychological stress are a major health care problem. Single-cell transcriptomics and lipidomic profiling in a mouse model of stress show that dermal fibroblasts undergoing adipogenesis have defective responses to <i>Staphylococcus aureus</i> skin infection. Adrenalectomy or adrenergic inhibition restores the fibroblast adipogenic response to <i>S. aureus</i> and enables mice to effectively resist infection during stress. Increased susceptibility to <i>S. aureus</i> from stress is attributed to suppression of the antimicrobial peptide cathelicidin (<i>Camp</i>) because adrenaline directly inhibits <i>Camp</i> production by fibroblasts, and mice lacking <i>Camp</i> in fibroblasts do not increase infection after stress. Transforming growth factor β (TGFβ) is induced by stress and adrenergic signaling, and inhibition of TGFβ or deletion of the TGFβ receptor on fibroblasts increases <i>Camp</i> expression and restores protection against infection. Together, these data show that stress initiates a brain-skin axis mediated by TGFβ that impairs the immune defense function of dermal fibroblasts to produce the Camp antimicrobial peptide.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 106","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.ads0519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Luck gone cold: A trifecta of B cell mutations associates with cryoglobulinemia","authors":"Kangzhi Chen, Kevin C. O’Connor","doi":"10.1126/sciimmunol.adx6827","DOIUrl":"10.1126/sciimmunol.adx6827","url":null,"abstract":"<div >Triple somatic mutations in autoreactive B cells contribute to virus-associated autoimmune disease.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 106","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel A. Waizman, Isabela Brown-Soler, Anjelica L. Martin, Yifan Ma, Kenneth Zhou, Kavita Israni-Winger, Cuiling Zhang, Ruslan Medzhitov, Pierre Launay, Michaël F. Michieletto, Jorge Henao-Mejia, Noah W. Palm, Joe Craft, Anna Eisenstein, Andrew Wang
{"title":"Skin damage signals mediate allergic sensitization to spatially unlinked antigen","authors":"Daniel A. Waizman, Isabela Brown-Soler, Anjelica L. Martin, Yifan Ma, Kenneth Zhou, Kavita Israni-Winger, Cuiling Zhang, Ruslan Medzhitov, Pierre Launay, Michaël F. Michieletto, Jorge Henao-Mejia, Noah W. Palm, Joe Craft, Anna Eisenstein, Andrew Wang","doi":"10.1126/sciimmunol.adn0688","DOIUrl":"10.1126/sciimmunol.adn0688","url":null,"abstract":"<div >Our current understanding of immunity to pathogens suggests that anatomic coupling of antigens with danger signals is a required feature for the formation of immune memory. However, in the context of pathogen-independent inflammation, the stringency of this anatomical coupling is unclear. Here, we demonstrate that multiple modes of skin injury were sufficient to induce a humoral response to antigens introduced in the gut. Skin damage induced a narrow subset of endocrine cytokines that were necessary and sufficient for the priming of antigens introduced at various distal tissues. Thus, in addition to “local priming” of antigen entering through damaged skin, there also exists another paradigm of “remote priming” where anatomical coupling is not essential because of the dissemination of damage-associated intermediaries. Our findings have implications for understanding the fundamental mechanisms of the formation of humoral memory with wide implications for diseases such as food allergy and in vaccinology.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 106","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariem Radhouani, Asma Farhat, Anna Hakobyan, Sophie Zahalka, Lisabeth Pimenov, Alina Fokina, Anastasiya Hladik, Karin Lakovits, Jessica Brösamlen, Vojtech Dvorak, Natalia Nunes, Andreas Zech, Marco Idzko, Thomas Krausgruber, Jörg Köhl, Ozge Uluckan, Jiri Kovarik, Kai Hoehlig, Axel Vater, Margret Eckhard, Andy Sombke, Nikolaus Fortelny, Jörg Menche, Sylvia Knapp, Philipp Starkl
{"title":"Eosinophil innate immune memory after bacterial skin infection promotes allergic lung inflammation","authors":"Mariem Radhouani, Asma Farhat, Anna Hakobyan, Sophie Zahalka, Lisabeth Pimenov, Alina Fokina, Anastasiya Hladik, Karin Lakovits, Jessica Brösamlen, Vojtech Dvorak, Natalia Nunes, Andreas Zech, Marco Idzko, Thomas Krausgruber, Jörg Köhl, Ozge Uluckan, Jiri Kovarik, Kai Hoehlig, Axel Vater, Margret Eckhard, Andy Sombke, Nikolaus Fortelny, Jörg Menche, Sylvia Knapp, Philipp Starkl","doi":"10.1126/sciimmunol.adp6231","DOIUrl":"10.1126/sciimmunol.adp6231","url":null,"abstract":"<div >Microbial exposure at barrier interfaces drives development and balance of the immune system, but the consequences of local infections for systemic immunity and secondary inflammation are unclear. Here, we show that skin exposure to the bacterium <i>Staphylococcus aureus</i> persistently shapes the immune system of mice with specific impact on progenitor and mature bone marrow neutrophil and eosinophil populations. The infection-imposed changes in eosinophils were long-lasting and associated with functional as well as imprinted epigenetic and metabolic changes. Bacterial exposure enhanced cutaneous allergic sensitization and resulted in exacerbated allergen-induced lung inflammation. Functional bone marrow eosinophil reprogramming and pulmonary allergen responses were driven by the alarmin interleukin-33 and the complement cleavage fragment C5a. Our study highlights the systemic impact of skin inflammation and reveals mechanisms of eosinophil innate immune memory and organ cross-talk that modulate systemic responses to allergens.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 106","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joao Paulo Cavalcanti de Albuquerque, Jenna Hunter, Rita G. Domingues, Erika Harno, Amy A. Worth, Fabrizio Maria Liguori, Aurora D’Alessio, Gabriella Aviello, David Bechtold, Anne White, Simon M. Luckman, Matthew R. Hepworth, Giuseppe D’Agostino
{"title":"Brain sensing of metabolic state regulates circulating monocytes","authors":"Joao Paulo Cavalcanti de Albuquerque, Jenna Hunter, Rita G. Domingues, Erika Harno, Amy A. Worth, Fabrizio Maria Liguori, Aurora D’Alessio, Gabriella Aviello, David Bechtold, Anne White, Simon M. Luckman, Matthew R. Hepworth, Giuseppe D’Agostino","doi":"10.1126/sciimmunol.adr3226","DOIUrl":"10.1126/sciimmunol.adr3226","url":null,"abstract":"<div >Changes in energy availability alter the dynamics of circulating immune cells. The existing view is that these effects are due to altered nutrient levels affecting peripheral tissue metabolism. Here, using mice and genetic approaches to manipulate the activity of distinct molecularly defined neurons, we show that the brain’s perception of hunger and satiety alone is sufficient to drive these immune changes. Hunger-promoting Agouti-related peptide (AgRP) neurons in the hypothalamus were both sufficient and necessary to reduce circulating Ly6C<sup>Hi</sup> classical monocytes during fasting. Mechanistically, these neurons suppressed hepatic mammalian target of rapamycin signaling via sympathetic regulation, decreasing circulating chemokine ligand 2 and monocyte numbers. AgRP neuron–induced corticosterone release and glucocorticoid receptor activation played a permissive role in this process. These changes in monocyte dynamics can occur independently of actual nutrient levels, revealing an unexpected brain-mediated control of peripheral immunity in response to perceived variation in energy state.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 106","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adr3226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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