# Sex Differences in Lung Immunity

**Authors:** Franz Puttur, Clare M. Lloyd

PMC · DOI: 10.1111/imr.70102 · 2026-02-15

## TL;DR

The paper discusses how biological sex influences lung immunity and disease susceptibility, emphasizing the need to consider sex in immunological research.

## Contribution

The paper highlights the importance of sex as a biological variable in lung immunology and suggests implications for sex-specific therapies.

## Key findings

- Sex differences in immune responses are evident in lung immunity and disease susceptibility.
- Environmental factors, genetics, and sex hormones collectively influence lung immune responses.
- Considering sex in research can lead to better understanding and treatment of lung diseases.

## Abstract

Biological sex has a significant impact on how the immune system develops and responds to foreign and self‐antigens. Sex differences exist in innate and adaptive immune cells, both at homeostasis and in the context of infection and inflammatory diseases such as asthma, cancer, and autoimmune disorders. Women generate stronger immune responses and are more susceptible to developing autoimmune conditions, while males are more prone to acute viral infections and developing certain cancers. Some immunological differences persist throughout life, while others emerge only after puberty and before reproductive senescence. Additionally, environmental exposures can affect the influence of biological sex in regulating immune function. This is particularly pertinent at mucosal surfaces such as the lungs, where lung immune defenses are constantly exposed to foreign material during respiration. Consequently, environmental factors together with genetics, age and sex hormones play a vital role in governing lung tissue immune responses between the sexes. In this context, we highlight studies that support the need for considering sex as an important biological variable in lung immunological research. This knowledge will provide a benchmark for understanding sex‐driven immunological mechanisms that underpin disease development and may inform new avenues targeted for generating sex‐specific therapies in lung disease.

## Linked entities

- **Diseases:** asthma (MONDO:0004979), cancer (MONDO:0004992)

## Full-text entities

- **Genes:** Hand2 (heart and neural crest derivatives expressed 2) [NCBI Gene 15111] {aka Ehand2, Hed, Th2, Thing2, bHLHa26, dHAND}, Cxcl9 (C-X-C motif chemokine ligand 9) [NCBI Gene 17329] {aka CMK, Mig, MuMIG, Scyb9, crg-10}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, DSP (desmoplakin) [NCBI Gene 1832] {aka DCWHKTA, DP}, RIEG2 (Rieger syndrome 2) [NCBI Gene 6012] {aka ARS, RGS2}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, Itgae (integrin alpha E, epithelial-associated) [NCBI Gene 16407] {aka A530055J10, CD103, aM290, alpha-E1, alpha-M290}, ZBED2 (zinc finger BED-type containing 2) [NCBI Gene 79413], AREG (amphiregulin) [NCBI Gene 374] {aka AR, AREGB, CRDGF, SDGF}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, SHBG (sex hormone binding globulin) [NCBI Gene 6462] {aka ABP, SBP, TEBG}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 17395] {aka B/MMP9, Clg4b, Gel B, MMP-9, pro-MMP-9}, Esr2 (estrogen receptor 2 (beta)) [NCBI Gene 13983] {aka ER[b], ERbeta, Estrb}, XIST (X inactive specific transcript) [NCBI Gene 7503] {aka DXS1089, DXS399E, LINC00001, NCRNA00001, SXI1, swd66}, Fdxr (ferredoxin reductase) [NCBI Gene 14149] {aka AR}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Cftr (cystic fibrosis transmembrane conductance regulator) [NCBI Gene 12638] {aka Abcc7}, Mir30a (microRNA 30a) [NCBI Gene 387225] {aka Mirn30a, mir-30a, mmu-mir-30a}, Pgr (progesterone receptor) [NCBI Gene 18667] {aka 9930019P03Rik, NR3C3, PR, PR-A, PR-B}, Slpi (secretory leukocyte peptidase inhibitor) [NCBI Gene 20568] {aka ALP}, LOC105243590 (Ig heavy chain Mem5-like) [NCBI Gene 105243590] {aka IgH, Igg1}, Ace2 (angiotensin converting enzyme 2) [NCBI Gene 70008] {aka 2010305L05Rik}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, Ar (androgen receptor) [NCBI Gene 11835] {aka Tfm}, Il1rl1 (interleukin 1 receptor-like 1) [NCBI Gene 17082] {aka DER4, Fit-1, Ly84, ST2L, St2, St2-rs1}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Crp (C-reactive protein, pentraxin-related) [NCBI Gene 12944], PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, Ccr2 (C-C motif chemokine receptor 2) [NCBI Gene 12772] {aka Cc-ckr-2, Ccr2a, Ccr2b, Ckr2, Ckr2a, Ckr2b}, Il13 (interleukin 13) [NCBI Gene 16163] {aka Il-13}, THBS1 (thrombospondin 1) [NCBI Gene 7057] {aka THBS, THBS-1, TSP, TSP-1, TSP1}, 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}, USP11 (ubiquitin specific peptidase 11) [NCBI Gene 8237] {aka UHX1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Egf (epidermal growth factor) [NCBI Gene 13645], Serpinb1-ps1 (serine (or cysteine) peptidase inhibitor, clade B, member 1, pseudogene) [NCBI Gene 282665] {aka EID, ovalbumin}, IL2RB (interleukin 2 receptor subunit beta) [NCBI Gene 3560] {aka CD122, IL15RB, IMD63, P70-75}, Csf1 (colony stimulating factor 1 (macrophage)) [NCBI Gene 12977] {aka BAP025, Csfm, MCSF, Mhdabap25, PG-M-CSF, op}, Ccl3 (C-C motif chemokine ligand 3) [NCBI Gene 20302] {aka G0S19-1, LD78alpha, MIP-1alpha, MIP1-(a), MIP1-alpha, Mip1a}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Tlr2 (toll-like receptor 2) [NCBI Gene 24088] {aka Ly105}, Cxcl2 (C-X-C motif chemokine ligand 2) [NCBI Gene 20310] {aka CINC-2a, GROb, Gro2, MIP-2, MIP-2a, Mgsa-b}, Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}
- **Diseases:** cognitive impairment (MESH:D003072), LUSC (MESH:D002294), NSCLC (MESH:D002289), systemic lupus erythematosus (MESH:D008180), -cell dysfunction (MESH:D002292), valve calcification (MESH:C562942), pulmonary hypertension (MESH:D006976), SARS-CoV2 (MESH:D045169), LC (MESH:D000094024), systemic disease (MESH:D034721), immune dysregulation (OMIM:614878), genetic diseases (MESH:D030342), hepatocellular carcinoma (MESH:D006528), acute infection (MESH:D000208), RDS (MESH:D012128), fever (MESH:D005334), bronchiolitis (MESH:D001988), COPD (MESH:D029424), HDM (MESH:D000092542), chest tightness (MESH:D002637), ILD (MESH:D017563), atopy (MESH:C564133), prematurity (MESH:C536271), acute lung inflammation (MESH:D011014), Allergic airway diseases (MESH:D004342), M. tuberculosis  infection (MESH:D014376), cytokine storm (MESH:D000080424), respiratory condition (MESH:D012131), SA (MESH:D010698), Bacterial Infections (MESH:D001424), multiple-organ failure (MESH:D009102), Autoimmune disorders (MESH:D001327), wheeze (MESH:D012135), LUAD (MESH:D000077192), pulmonary hemorrhage (MESH:D006470), obese (MESH:D009765), AVS (MESH:D001024), hypoxic (MESH:D002534), CMV (MESH:D003586), pulmonary surfactant deficiency (MESH:C553654), cough (MESH:D003371), Bronchopulmonary Dysplasia (MESH:D001997), CF (MESH:D003550), androgen insensitivity syndrome (MESH:D013734), emphysema (MESH:D004646), Asthma (MESH:D001249), decline in lung function (MESH:D055370), anxiety (MESH:D001007), preterm infants (MESH:D047928), RSV infection (MESH:D018357), infected (MESH:D007239), cardiovascular disease (MESH:D002318), Lung Cancer (MESH:D008175), infants (MESH:D063766), shortness of breath (MESH:D004417), IPF (MESH:D054990), impairments in physiological functioning (MESH:D012735), diabetes (MESH:D003920), COVID-19 (MESH:D000086382), Lung diseases (MESH:D008171)
- **Chemicals:** methicillin (MESH:D008712), nintedanib (MESH:C530716), nitric oxide (MESH:D009569), short-chain fatty acids (MESH:D005232), calcium (MESH:D002118), polycyclic aromatic hydrocarbon (MESH:D011084), ROS (MESH:D017382), Progesterone (MESH:D011374), bleomycin (MESH:D001761), ICI-182,780 (MESH:D000077267), DHT (MESH:D013196), Cellulose (MESH:D002482), lipid (MESH:D008055), testosterone (MESH:D013739), steroid (MESH:D013256), beta-lactam antibiotic (MESH:D008997), fatty-acid (MESH:D005227), pirfenidone (MESH:C093844), pectin (MESH:D010368), 17beta-estradiol (MESH:D004958), gefitinib (MESH:D000077156), aztreonam (MESH:D001398), salt (MESH:D012492), oxygen (MESH:D010100), ozone (MESH:D010126), superoxide (MESH:D013481), 17B-estradiol (-), DMPA (MESH:C050795), medroxyprogesterone acetate (MESH:D017258), vitamin D (MESH:D014807)
- **Species:** gut metagenome (species) [taxon 749906], Nicotiana tabacum (American tobacco, species) [taxon 4097], H1N1 subtype (serotype) [taxon 114727], Influenza A virus (no rank) [taxon 11320], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Haemophilus influenzae (species) [taxon 727], Mycobacterium tuberculosis variant bovis BCG (no rank) [taxon 33892], Homo sapiens (human, species) [taxon 9606], Staphylococcus aureus (species) [taxon 1280], Stenotrophomonas (genus) [taxon 40323], Mycobacterium tuberculosis (species) [taxon 1773], Mus musculus (house mouse, species) [taxon 10090], Pseudomonas aeruginosa (species) [taxon 287], H3N1 subtype (serotype) [taxon 157802], Bacillus sp. CG (species) [taxon 1196795], H7N9 subtype (serotype) [taxon 333278], Pseudomonas putida (species) [taxon 303], Streptococcus (genus) [taxon 1301], Respiratory syncytial virus (no rank) [taxon 12814]
- **Mutations:** F508del
- **Cell lines:** BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12907607/full.md

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Source: https://tomesphere.com/paper/PMC12907607