# The role of Piezo1 in immune cells and pregnancy **Authors:** Yiming Fei, Yilin Liu, Lijuan Zhang PMC · DOI: 10.3389/fimmu.2026.1748854 · Frontiers in Immunology · 2026-02-18 ## TL;DR This paper reviews how the Piezo1 ion channel affects immune cell function and plays a key role in maintaining pregnancy and labor. ## Contribution This review systematically compiles Piezo1's roles in immune regulation and pregnancy, highlighting its potential as a therapeutic target. ## Key findings - Piezo1 modulates innate and adaptive immune cell functions, including macrophage polarization and T cell mechanosensation. - Piezo1 regulates calcium signaling and vascular changes during pregnancy, impacting implantation and labor onset. - Targeting Piezo1 may offer therapeutic strategies for pregnancy-related disorders. ## Abstract In innate immunity, Piezo1 influences macrophage polarization, neutrophil migration, inflammation and repair. In adaptive immunity, it modulates T cell mechanosensation, immune synapse formation and B cell antigen presentation. Expressed in endometrium, placental vasculature, placental trophoblast and myometrium, Piezo1 regulates Ca²+ signaling during implantation, NO-dependent placental vasodilation, uterine contractions and inflammation, impacting pregnancy maintenance and labor onset. This review systematically summarizes the pivotal role of the mechanosensitive ion channel Piezo1 in immunoregulation and pregnancy. Firstly, it outlines the molecular structure of Piezo1 alongside its activation and inactivation mechanisms. Secondly, it focuses on Piezo1’s functions within innate and adaptive immune cells (such as macrophages and T cells) and its regulation of immune responses. Subsequently, it delves into Piezo1’s pivotal role across multiple stages of pregnancy, including its influence on uteroplacental vascular remodeling, trophoblast cell fusion, labor initiation, and fetal development. Particular attention is given to its potential bridging function linking immune homeostasis with successful pregnancy. Finally, it outlines the therapeutic potential of targeting Piezo1 in related pregnancy disorders and future research directions. This paper aims to provide insights into the integrated function of mechanobiology within reproductive immunity. ## Linked entities - **Genes:** PIEZO1 (piezo type mechanosensitive ion channel component 1 (Er blood group)) [NCBI Gene 9780] ## Full-text entities - **Genes:** NOX4 (NADPH oxidase 4) [NCBI Gene 50507] {aka KOX, KOX-1, RENOX}, PIEZO1 (piezo type mechanosensitive ion channel component 1 (Er blood group)) [NCBI Gene 9780] {aka DHS, ER, FAM38A, LMPH3, LMPHM6, Mib}, ETS1 (ETS proto-oncogene 1, transcription factor) [NCBI Gene 2113] {aka ETS-1, EWSR2, c-ets-1, p54}, MAFG (MAF bZIP transcription factor G) [NCBI Gene 4097] {aka hMAF}, MYOD1 (myogenic differentiation 1) [NCBI Gene 4654] {aka CMYO17, CMYP17, MYF3, MYOD, MYODRIF, PUM}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, RNF114 (ring finger protein 114) [NCBI Gene 55905] {aka PSORS12, ZNF313}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, SMPD3 (sphingomyelin phosphodiesterase 3) [NCBI Gene 55512] {aka NSMASE2}, CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919] {aka FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MDFIC (MyoD family inhibitor domain containing) [NCBI Gene 29969] {aka HIC, LMPHM12, MDFIC1}, CSF3 (colony stimulating factor 3) [NCBI Gene 1440] {aka C17orf33, CSF3OS, GCSF}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CTSS (cathepsin S) [NCBI Gene 1520], TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, FOSB (FosB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2354] {aka AP-1, G0S3, GOS3, GOSB}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, ANO6 (anoctamin 6) [NCBI Gene 196527] {aka BDPLT7, SCTS, TMEM16F}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CD69 (CD69 molecule) [NCBI Gene 969] {aka AIM, BL-AC/P26, CLEC2C, EA1, GP32/28, MLR-3}, CAMK2G (calcium/calmodulin dependent protein kinase II gamma) [NCBI Gene 818] {aka CAMK, CAMK-II, CAMKG, MRD59}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, ACSL4 (acyl-CoA synthetase long chain family member 4) [NCBI Gene 2182] {aka ACS4, FACL4, LACS4, MRX63, MRX68, XLID63}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, 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}, SGK1 (serum/glucocorticoid regulated kinase 1) [NCBI Gene 6446] {aka SGK}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, ITGAL (integrin subunit alpha L) [NCBI Gene 3683] {aka CD11A, EV6, HNA-5, LFA-1, LFA1A}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, ZAP70 (zeta chain of T cell receptor associated protein kinase 70) [NCBI Gene 7535] {aka ADMIO2, IMD48, SRK, STCD, STD, TZK}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, MDFI (MyoD family inhibitor) [NCBI Gene 4188] {aka I-MF, I-mfa}, CXADRP1 (CXADR pseudogene 1) [NCBI Gene 653108] {aka CAR, CXADRP}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, Piezo1 (piezo-type mechanosensitive ion channel component 1) [NCBI Gene 234839] {aka 9630020g22, Fam38a, mKIAA0233}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, APLN (apelin) [NCBI Gene 8862] {aka APEL, XNPEP2}, OSR2 (odd-skipped related transciption factor 2) [NCBI Gene 116039], YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, NFATC2 (nuclear factor of activated T cells 2) [NCBI Gene 4773] {aka JCOSL, NFAT1, NFATP}, TRPV4 (transient receptor potential cation channel subfamily V member 4) [NCBI Gene 59341] {aka BCYM3, CMT2C, HMSN2C, OTRPC4, SMAL, SPSMA} - **Diseases:** complications (MESH:D008107), embryonic lethality (MESH:D020964), placental insufficiency (MESH:D010927), inflammation (MESH:D007249), lung infections (MESH:D012141), degenerative diseases (MESH:D019636), FGR (MESH:D005317), metastasis (MESH:D009362), thrombosis (MESH:D013927), epilepsy (MESH:D004827), iron overload (MESH:D019190), T cell lymphoma (MESH:D016399), fibrosis (MESH:D005355), hereditary polycythemia (MESH:D009386), hypertension (MESH:D006973), developmental abnormalities (MESH:D006130), mitochondrial damage (MESH:D028361), tendon injury (MESH:D013708), pregnancy complications (MESH:D011248), atherosclerosis (MESH:D050197), SAH (MESH:D013345), infections (MESH:D007239), DHS (MESH:C566369), preterm birth (MESH:D047928), AD (MESH:D000544), lymphedema (MESH:D008209), colitis (MESH:D003092), Tumor (MESH:D009369), PL (OMIM:614338), RM (MESH:D000026), immune diseases (MESH:D007154), PAS (MESH:D010922), ischemic (MESH:D002545), endothelial dysfunction (MESH:D014652), cytotoxicity (MESH:D064420), liver/kidney fibrosis (MESH:D008103), vascular dysfunction (MESH:D002561), EPE (MESH:D011225), GVHD (MESH:D006086), myopia (MESH:D009216), neuroinflammation (MESH:D000090862), Hydrops (MESH:D004487), labor (MESH:D048949), asthma (MESH:D001249), pleural effusion (MESH:D010996), macrocytic anemia (MESH:D000748), neuronal damage (MESH:D009410), lymphatic (MESH:D008206), heterotopic ossification (MESH:D009999), aortic valve stenosis (MESH:D001024), EAE (MESH:D004681), autoimmune diseases (MESH:D001327), TAM (MESH:D020914), liver damage (MESH:D056486), lung inflammation (MESH:D011014), skin carcinogenesis (MESH:D063646), fetal (MESH:D005315), NIHF (MESH:D015160), PMF (MESH:D055728), hereditary diseases (MESH:D030342) - **Chemicals:** CAQKERM@GsMTx4 (-), Yoda1 (MESH:C000708435), NO (MESH:D009614), sodium (MESH:D012964), ionomycin (MESH:D015759), Dexamethasone (MESH:D003907), phosphatidylserine (MESH:D010718), lipid (MESH:D008055), AA (MESH:D016718), LPS (MESH:D008070), ruthenium red (MESH:D012430), NO (MESH:D009569), glucose (MESH:D005947), ceramide (MESH:D002518), calcium (MESH:D002118), chloride (MESH:D002712) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606] - **Mutations:** E756del - **Cell lines:** HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12956649/full.md ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12956649/full.md ## References 164 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956649/full.md --- Source: https://tomesphere.com/paper/PMC12956649