# Sex differences in immune cells: mechanistic perspectives and clinical correlates in physiology and disease

**Authors:** Ximing Liao, Di Wu, Jing Gao, Fengyang Xie, Zhaoqi Li, Muyun Wang, Kun Wang, Yixuan Gao, Qiang Li, Wei Gao

PMC · DOI: 10.3389/fimmu.2026.1650527 · Frontiers in Immunology · 2026-02-17

## TL;DR

This review explores how sex differences affect immune cells and their roles in health and disease, aiming to improve sex-specific precision medicine.

## Contribution

The paper provides a comprehensive overview of how sex influences immune regulation through hormones and chromosomes.

## Key findings

- Sex hormones and chromosomes significantly modulate immune cell function and fate.
- Sex differences contribute to variations in disease epidemiology and therapeutic response.
- Understanding these differences can lead to sex-specific precision medicine strategies.

## Abstract

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.

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, XIST (X inactive specific transcript) [NCBI Gene 7503] {aka DXS1089, DXS399E, LINC00001, NCRNA00001, SXI1, swd66}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 19225] {aka COX2, Cox-2, PES-2, PGHS-2, PHS II, PHS-2}, Hmgb1 (high mobility group box 1) [NCBI Gene 15289] {aka HMG-1, Hmg1, SBP-1, p30}, Cxcl5 (C-X-C motif chemokine ligand 5) [NCBI Gene 20311] {aka AMCF-II, Cxcl6, ENA-78, GCP-2, LIX, Scyb5}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, HSD17B13 (hydroxysteroid 17-beta dehydrogenase 13) [NCBI Gene 345275] {aka FLDP, HMFN0376, NIIL497, SCDR9, SDR16C3}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, Sry (sex determining region of Chr Y) [NCBI Gene 21674] {aka Tdf, Tdy}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, Il1rl1 (interleukin 1 receptor-like 1) [NCBI Gene 17082] {aka DER4, Fit-1, Ly84, ST2L, St2, St2-rs1}, CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 820] {aka CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26}, Gca (grancalcin) [NCBI Gene 227960] {aka 5133401E04Rik}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Serpinb1-ps1 (serine (or cysteine) peptidase inhibitor, clade B, member 1, pseudogene) [NCBI Gene 282665] {aka EID, ovalbumin}, Foxo1 (forkhead box O1) [NCBI Gene 56458] {aka Afxh, FKHR, Fkhr1, Foxo1a}, TLR8 (toll like receptor 8) [NCBI Gene 51311] {aka CD288, IMD98, TLR-8, hTLR8}, Cxcl12 (C-X-C motif chemokine ligand 12) [NCBI Gene 20315] {aka Pbsf, Scyb12, Sdf1, Tlsf, Tpar1}, Il33 (interleukin 33) [NCBI Gene 77125] {aka 9230117N10Rik, Il-33, Il1f11, NF-HEV}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, Bcr (BCR activator of RhoGEF and GTPase) [NCBI Gene 110279] {aka 5133400C09Rik, mKIAA3017}, Cxcl2 (C-X-C motif chemokine ligand 2) [NCBI Gene 20310] {aka CINC-2a, GROb, Gro2, MIP-2, MIP-2a, Mgsa-b}, Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 14825] {aka Fsp, Gro1, KC, Mgsa, N51, Scyb1}, Paqr8 (progestin and adipoQ receptor family member VIII) [NCBI Gene 74229] {aka 1700019B16Rik, 3110001D06Rik, mPR beta}, Irf8 (interferon regulatory factor 8) [NCBI Gene 15900] {aka ICSBP, IRF-8, Icsbp1, Myls}, S100a6 (S100 calcium binding protein A6 (calcyclin)) [NCBI Gene 20200] {aka 2A9, 5B10, CALCYCLIN, Cacy, PRA}, Panx1 (pannexin 1) [NCBI Gene 55991], Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Crh (corticotropin releasing hormone) [NCBI Gene 12918] {aka CRF, Gm1347}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Ccr2 (C-C motif chemokine receptor 2) [NCBI Gene 12772] {aka Cc-ckr-2, Ccr2a, Ccr2b, Ckr2, Ckr2a, Ckr2b}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, GNAQ (G protein subunit alpha q) [NCBI Gene 2776] {aka CMAL, G-ALPHA-q, GAQ, SWS}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, Il23a (interleukin 23, alpha subunit p19) [NCBI Gene 83430] {aka IL-23, p19}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Slurp1 (secreted Ly6/Plaur domain containing 1) [NCBI Gene 57277] {aka 1110021N19Rik, ARS, ArsB, Slurp-1}, Gpr34 (G protein-coupled receptor 34) [NCBI Gene 23890] {aka Lypsr1}, Cyp17a1 (cytochrome P450, family 17, subfamily a, polypeptide 1) [NCBI Gene 13074] {aka Cyp17, p450c17}, Sgk1 (serum/glucocorticoid regulated kinase 1) [NCBI Gene 20393] {aka Sgk}, Esr1 (estrogen receptor 1 (alpha)) [NCBI Gene 13982] {aka ER, ER-alpha, ERa, ERalpha, ESR, Estr}, Cyp19a1 (cytochrome P450, family 19, subfamily a, polypeptide 1) [NCBI Gene 13075] {aka Ar, ArKO, Cyp19, Int-5, Int5, p450arom}, Itgae (integrin alpha E, epithelial-associated) [NCBI Gene 16407] {aka A530055J10, CD103, aM290, alpha-E1, alpha-M290}, Esr2 (estrogen receptor 2 (beta)) [NCBI Gene 13983] {aka ER[b], ERbeta, Estrb}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, Fdxr (ferredoxin reductase) [NCBI Gene 14149] {aka AR}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 17395] {aka B/MMP9, Clg4b, Gel B, MMP-9, pro-MMP-9}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Cxcr2 (C-X-C motif chemokine receptor 2) [NCBI Gene 12765] {aka CD128, CDw128, Cmkar2, Gpcr16, IL-8Rh, IL-8rb}, IL1R1 (interleukin 1 receptor type 1) [NCBI Gene 3554] {aka CD121A, CRMO3, D2S1473, IL-1R-alpha, IL-1RT1, IL1R}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}
- **Diseases:** atherosclerotic plaque (MESH:D058226), necrotic (MESH:D009336), mechanical allodynia (MESH:D006930), tissue injury (MESH:D017695), glioblastoma (MESH:D005909), bladder cancer (MESH:D001749), infectious (MESH:D003141), estrogen deficiency (MESH:D056828), Breast Cancer (MESH:D001943), adipose (MESH:D018205), chronic pain (MESH:D059350), autoimmune encephalomyelitis (MESH:D004681), pregnancy loss (MESH:D000022), neuropathic pain (MESH:D009437), inflammatory liver injury (MESH:D017093), allergic (MESH:D004342), associated (MESH:D018886), pulmonary fibrosis (MESH:D011658), type 1 diabetes (MESH:D003922), infected (MESH:D007239), myocardial infarction (MESH:D009203), Crohn's disease (MESH:D003424), encephalomyelitis (MESH:D004679), colitis (MESH:D003092), allergic rhinitis (MESH:D065631), coronavirus disease 2019 (MESH:D000086382), cytotoxicity (MESH:D064420), juvenile idiopathic arthritis (MESH:D001171), urinary tract infection (MESH:D014552), bone loss (MESH:D001847), arthritis (MESH:D001168), rheumatoid arthritis (MESH:D001172), neutropenia (MESH:D009503), hypertension (MESH:D006973), Streptococcus agalactiae (MESH:D011008), leukemia (MESH:D007938), viral infection (MESH:D014777), metabolic disease (MESH:D008659), acute myeloid leukemia (MESH:D015470), ischemia (MESH:D007511), psoriasis (MESH:D011565), acute (MESH:D000208), ARDS (MESH:D012128), SLE (MESH:D008180), systemic sclerosis (MESH:D012595), anaphylaxis (MESH:D000707), mammary tumor (MESH:D015674), NETs (MESH:C536657), steatohepatitis (MESH:D005234), obese (MESH:D009765), inhalation lung injury (MESH:D015208), microbial infections (MESH:D015163), castration (MESH:D064129), autoimmune diseases (MESH:D001327), Amebic liver abscess (MESH:D008101), pneumococcal pneumonia (MESH:D011018), cerebral aneurysm rupture (MESH:D017542), lung inflammation (MESH:D011014), myocarditis (MESH:D009205), neurotoxic (MESH:D020258)
- **Chemicals:** Dihydrotestosterone (MESH:D013196), imiquimod (MESH:D000077271), ROS (MESH:D017382), steroid hormones (MESH:D013256), allopregnanolone (MESH:D011280), DHEA (MESH:D003687), LPS (MESH:D008070), leukotriene (MESH:D015289), Cl2 (MESH:D002713), estriol (MESH:D004964), DT (MESH:D013936), Ca2+ (-), NO (MESH:D009614), Progesterone (MESH:D011374), cholesterol (MESH:D002784), Nitric oxide (MESH:D009569), estrone (MESH:D004970), arachidonic acid (MESH:D016718), Testosterone (MESH:D013739), 17alpha-hydroxypregnenolone (MESH:D006907), E2 (MESH:D004958), prostaglandin (MESH:D011453), androstenedione (MESH:D000735), Pregnenolone (MESH:D011284), fat (MESH:D005223), histamine (MESH:D006632), T (MESH:D014316), P (MESH:D010758)
- **Species:** Coxiella burnetii (species) [taxon 777], Cavia porcellus (domestic guinea pig, species) [taxon 10141], Staphylococcus aureus (species) [taxon 1280], Rattus norvegicus (brown rat, species) [taxon 10116], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Homo sapiens (human, species) [taxon 9606], Respiratory syncytial virus (no rank) [taxon 12814], Coxsackievirus B3 (no rank) [taxon 12072], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12953550/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12953550/full.md

## References

188 references — full list in the complete paper: https://tomesphere.com/paper/PMC12953550/full.md

---
Source: https://tomesphere.com/paper/PMC12953550