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REVIEW article

Front. Immunol.

Sec. Molecular Innate Immunity

Sex Differences in Immune Cells: Mechanistic Perspectives and Clinical Correlates in Physiology and Disease

Provisionally accepted
Ximing LiaoXiming Liao1Di WuDi Wu1Jing GaoJing Gao1Fengyang XieFengyang Xie2Zhaoqi LiZhaoqi Li3Wang MuyunWang Muyun1Kun WangKun Wang1Yixuan GaoYixuan Gao4*Qiang LiQiang Li1*Wei GaoWei Gao1*
  • 1Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
  • 2Shanghai Jing'an District Caojiadu Community Health Center, Shanghai, China
  • 3Saint George’s University, West Indies, Grenada
  • 4Shandong Provincial Hospital, Jinan, China

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For decades, sex disparities have been acknowledged to influence immune regulation in health and disease throughout the life span, and contribute to variations in epidemiology, pathophysiology, manifestation, progression, and therapeutic response in multiple disorders. However, the underlying cellular and molecular mechanisms governing these disparities remain understudied. This review articulates the effects of sex as critical regulators of the major causes of morbidity and mortality in diseases. We summarize the key factors driving sex differences, including sexual hormones and sex chromosomes, as well as elaborate how these factors influence physiology and disease, especially by modulating the function and fate of immune cells. Our aim is to disentangle the intricacies of sexually-differentiated immune responses within physiological and pathological contexts, thereby establishing the groundwork for precision medicine approaches customized to sex-specific requirements in clinical settings.

Keywords: Disease, immune cells, Physiology, Sex disparity, Sexual hormone

Received: 18 Jan 2026; Accepted: 31 Jan 2026.

Copyright: © 2026 Liao, Wu, Gao, Xie, Li, Muyun, Wang, Gao, Li and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yixuan Gao
Qiang Li
Wei Gao

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material