# Immunomodulatory therapy for sepsis: from pathophysiological mechanisms to precision treatment **Authors:** Yiting Xiao, Liyun Xu, Yuan Jiang, Qian Wang, Jie Deng, Zixiang Luo, Wenchao Xie, Caihong Ye, Zhangrui Zeng PMC · DOI: 10.3389/fcimb.2025.1746254 · Frontiers in Cellular and Infection Microbiology · 2026-02-11 ## TL;DR This review discusses how understanding immune mechanisms in sepsis can lead to better, personalized treatments using advanced technologies. ## Contribution The paper proposes a precision medicine framework integrating multi-omics and bioengineering for sepsis treatment. ## Key findings - Sepsis involves immune dysregulation from hyperinflammation to immunosuppression. - Dynamic biomarker monitoring and immune endotyping can improve personalized sepsis management. - Single-cell technologies and machine learning may guide stage-specific immunotherapies. ## Abstract Sepsis is a life-threatening syndrome marked by immune dysregulation, progressing from hyperinflammation to immunosuppression. The translation of immunomodulatory therapies has been hampered by the disease’s extreme heterogeneity. This review synthesizes current progress and future perspectives in sepsis immunotherapy. We outline key immunopathological mechanisms and critically discuss evolving diagnostic tools, including dynamic biomarker monitoring and immune endotyping for personalized management. We then highlight novel therapeutic targets and explore how integrating single-cell technologies, dynamic profiling, and machine learning can guide stage-specific, precision treatment. Ultimately, a precision medicine framework combining multi-omics data with advanced bioengineering may offer new avenues to overcome the therapeutic impasse in sepsis. ## Full-text entities - **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TFEB (transcription factor EB) [NCBI Gene 7942] {aka ALPHATFEB, BHLHE35, TCFEB}, CXADRP1 (CXADR pseudogene 1) [NCBI Gene 653108] {aka CAR, CXADRP}, TLR3 (toll like receptor 3) [NCBI Gene 7098] {aka CD283, IIAE2, IMD83}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, TICAM1 (TIR domain containing adaptor molecule 1) [NCBI Gene 148022] {aka IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, RIGI (RNA sensor RIG-I) [NCBI Gene 23586] {aka DDX58, RIG-I, RIG1, RLR-1, SGMRT2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, HEBP1 (heme binding protein 1) [NCBI Gene 50865] {aka HBP, HEBP}, ULK1 (unc-51 like autophagy activating kinase 1) [NCBI Gene 8408] {aka ATG1, ATG1A, UNC51, Unc51.1, hATG1}, CYP1A1 (cytochrome P450 family 1 subfamily A member 1) [NCBI Gene 1543] {aka AHH, CP11, CYP1, CYPIA1, P1-450, P450-C}, GAS6 (growth arrest specific 6) [NCBI Gene 2621] {aka AXLLG, AXSF}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CLEC7A (C-type lectin domain containing 7A) [NCBI Gene 64581] {aka BGR, CANDF4, CD369, CLECSF12, DECTIN1, SCARE2}, AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, HAVCR2 (hepatitis A virus cellular receptor 2) [NCBI Gene 84868] {aka CD366, HAVcr-2, KIM-3, SPTCL, TIM3, TIMD-3}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, TNFRSF1B (TNF receptor superfamily member 1B) [NCBI Gene 7133] {aka CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B}, SIRT3 (sirtuin 3) [NCBI Gene 23410] {aka SIR2L3}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, LY96 (lymphocyte antigen 96) [NCBI Gene 23643] {aka ESOP-1, MD-2, MD2, ly-96}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, MIR146A (microRNA 146a) [NCBI Gene 406938] {aka MIRN146, MIRN146A, miR-146a, miRNA146A}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) [NCBI Gene 3156] {aka LDLCQ3, LGMDR28, MYPLG}, AXL (AXL receptor tyrosine kinase) [NCBI Gene 558] {aka ARK, AXL3, JTK11, Tyro7, UFO}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF} - **Diseases:** organ dysfunction (MESH:D009102), hypoxic (MESH:D002534), leukopenia (MESH:D007970), metabolic dysregulation (MESH:D021081), trauma (MESH:D014947), inflammation (MESH:D007249), mitochondrial dysfunction (MESH:D028361), influenza (MESH:D007251), lymphopenia (MESH:D008231), cancer (MESH:D009369), pancreatitis (MESH:D010195), cytokine storm (MESH:D000080424), Bacterial (MESH:D001424), septic (MESH:D001170), immune dysregulation (OMIM:614878), storm (MESH:C566109), septic shock (MESH:D012772), Sepsis (MESH:D018805), RAI (MESH:D059446), tissue injury (MESH:D017695), viral infections (MESH:D014777), COVID-19 (MESH:D000086382), immunological disorders (MESH:D007154), infection (MESH:D007239), leukocytosis (MESH:D007964) - **Chemicals:** kynurenine (MESH:D007737), rapamycin (MESH:D020123), A769662 (MESH:C512408), LPS (MESH:D008070), tryptophan (MESH:D014364), nivolumab (MESH:D000077594), beta-glucan (MESH:D047071), Chimeric antigen receptor-macrophage (-), AICAR (MESH:C031143), phosphatidylinositol (3,4,5)-trisphosphate (MESH:C060974) - **Species:** Homo sapiens (human, species) [taxon 9606] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12932498/full.md ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932498/full.md ## References 63 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932498/full.md --- Source: https://tomesphere.com/paper/PMC12932498