Cancer persists as a leading global cause of mortality. Within this complex landscape, transcription factors (TFs) are pivotal drivers, orchestrating tumor cell phenotypic plasticity and remodeling the immunosuppressive tumor microenvironment through downstream gene regulation. Beyond its established roles in embryonic development and angiogenesis, the SOX (SRY-related HMG-box) family member SOX18 has now been implicated as a critical oncogenic player. Mounting evidence reveals SOX18 overexpression across diverse malignancies, where it actively drives key malignant hallmarks including tumor initiation, metastatic progression, and immune evasion. This review synthesizes the latest advances elucidating the multifaceted roles of SOX18 in cancer pathogenesis. Our aim is to highlight SOX18’s potential as a novel therapeutic target and guide the development of innovative intervention strategies to optimize clinical cancer management.

Liver cancer remains one of the leading causes of cancer-related death worldwide, and its immunologically "cold" tumor microenvironment continues to undermine the efficacy of immunotherapy. Among the many stroma-derived factors, C-X-C motif chemokine ligand 12 (CXCL12) is regarded as a central regulator of immune exclusion, mediating limited effector T cell infiltration and promoting tumor progression through C-X-C chemokine receptor type (CXCR) 4 and CXCR7. This review summarizes the latest understanding of the CXCL12-CXCR4/CXCR7 axis in liver cancer, with particular emphasis on the new perspective that cancer-associated fibroblast (CAF) heterogeneity shapes distinct CXCL12 niches, and that CXCL12 constructs a spatial barrier at the tumor margin to reinforce immune privilege. We further evaluate therapeutic strategies targeting this axis, including antagonists, neutralizing antibodies, and novel delivery systems, and explore their combination with immune checkpoint inhibitors (ICIs), emerging immunotherapies, and anti-angiogenic treatments. In addition, we propose the clinical potential of CXCL12-CXCR4/CXCR7 axis-related molecules as predictive biomarkers, highlighting the translational value of resistance mechanisms and immune re-sensitization. Through these new perspectives, this review provides an innovative summary and future research directions for understanding the key role of CXCL12 in the liver cancer immune microenvironment and for developing targeted combination immunotherapy strategies.

Persistent inflammation impedes peripheral nerve regeneration, in which infiltrating macrophages play pivotal roles by regulating the M1/M2 phenotypic balance. M2 macrophages facilitate repair, yet factors driving M1-to-M2 transition remain unclear. Lactate, a key metabolic byproduct in injured tissue, dynamically regulates microenvironmental signaling. Here, we observed a correlation between M2 macrophage accumulation and lactate elevation within 5 days post-sciatic nerve injury. In vitro, both Schwann cells and macrophages were identified as important lactate producers. In vivo, low-dose lactate (10-20 mM) enhanced M2 polarization and accelerated regeneration, whereas high-dose lactate (50 mM) showed no benefit. Transcriptomic analysis revealed that 10 mM lactate upregulated M2 markers (arginase 1 (Arg1), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β)) and oxidative phosphorylation (OXPHOS)-related genes in M1 macrophages. Seahorse analysis and adenosine triphosphate (ATP) quantification confirmed lactate-driven OXPHOS activation. Conversely, 50 mM lactate induced excessive reactive oxygen species (ROS) and reduced mitochondrial membrane potential which may explain its lack of regenerative efficacy. Furthermore, CCAAT/enhancer-binding protein beta (Cebpb), a transcription factor can promote Arg1 and VEGF expression in M1 cells under 20 mM lactate. Our findings demonstrate that low-dose lactate promotes M1-to-M2 transition via OXPHOS metabolic reprogramming and Cebpb upregulation, whereas excessive lactate disrupts mitochondrial function. This highlights lactate concentration-dependent modulation of macrophage polarization, a finding that provides insights into metabolic regulation of inflammatory responses during nerve repair. The current data, which focus on macrophage polarization outcomes, support further investigation into whether targeting metabolic rewiring could optimize regenerative microenvironments for functional nerve regeneration.

Liver transplantation is the most effective treatment for end-stage liver disease and acute liver failure; however, organ shortage and transplant rejection remain key challenges limiting its development. In recent years, the unique role of immune cells in liver transplantation has provided new insights into the mechanisms of immune rejection and tolerance. The liver's unique immune microenvironment, dominated by innate immune cells, maintains immune tolerance through complex cell-cell interactions and cytokine networks. This article systematically reviews the dynamic roles of macrophages, neutrophils, dendritic cells (DCs), natural killer (NK) cells, and regulatory T cells (Tregs) in liver transplantation, as well as emerging therapeutic strategies derived from these findings, such as Treg infusion, machine perfusion technology, and immunometabolic regulation, all of which demonstrate immense potential. Further exploration of the heterogeneity of immune cells and their dynamic regulatory networks-particularly through the use of single-cell sequencing and spatial transcriptomics to elucidate the functional plasticity and dynamic switching mechanisms of immune cell subsets-will provide crucial guidance for achieving personalized induction of immune tolerance and optimizing liver transplant outcomes, while also laying the molecular foundation for the development of more targeted immune intervention strategies.

Tumor-associated macrophages (TAMs) are the core innate immune cells in the tumor microenvironment (TME), and their phenotypic polarization and functional reprogramming determine the orientation of the tumor immune microenvironment and the efficacy of immunotherapy. As a key intracellular second messenger, cyclic adenosine monophosphate (cAMP) acts as a central hub regulating TAM function by activating two major downstream effector pathways: protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). This article systematically reviews the molecular mechanisms by which the cAMP-PKA/Epac signaling pathway regulates TAMs, the upstream regulatory factors in the TME, and targeted tumor immunotherapy strategies for this pathway. Studies have shown that cAMP mainly induces TAMs to polarize toward a protumor "M2-like phenotype" through two classical pathways: cAMP-PKA-cyclic AMP response element-binding protein (CREB) and cAMP-PKA-signal transducer and activator of transcription 3/6 (STAT3/6). Meanwhile, it enhances the immunosuppressive, proangiogenic, and profibrotic functions of TAMs via the cAMP-Epac pathway, inhibition of nuclear factor kappa-B (NF-κB) signaling, and attenuation of M1 polarization. Furthermore, lactate and hypoxia-inducible factor-1α (HIF-1α) in the TME can further activate the intracellular cAMP signaling pathway in TAMs by activating G protein-coupled receptors (GPCRs) and regulating the expression of adenylate cyclase, forming a cascade regulatory network with cAMP that exacerbates tumor immunosuppression. In addition, targeting the cAMP metabolic process, the downstream PKA pathway, and key molecules such as CREB/STAT/NF-κB can effectively reverse the "M2-like phenotype" of TAMs and restore their antitumor functions. Combination with immune checkpoint inhibitors can also significantly enhance the efficacy of tumor immunotherapy. By summarizing the core mechanisms of the cAMP-TAM regulatory axis and targeted intervention strategies, this article provides theoretical references and potential target directions for the development of novel tumor immunotherapy regimens based on TAM reprogramming.

Gastric cancer (GC) ranks as the third leading cause of cancer-related mortality worldwide, and its management remains formidable. Immunotherapy has been highly praised for its remarkable efficacy and acceptable toxicity, and its development has outpaced that of traditional therapies. However, molecular heterogeneity and the immunosuppressive tumor immune microenvironment (TIME) have hindered the treatment response of a considerable number of patients. This review synthesizes the latest therapeutic advances, spanning immune-checkpoint inhibitors (ICIs), adoptive cell therapy (ACT), monoclonal antibodies and antibody drug conjugates (ADCs), cancer vaccines, tumor-infiltrating lymphocyte (TIL) therapy, and CAR-T cells therapy. Emerging strategies such as RNA interference nano-delivery systems, immune adjuvants, and microbiota modulation are constantly evolving to transform “cold” tumors into “hot” tumors. Persistent challenges include primary resistance, immune-related adverse events (irAEs) and antigenic heterogeneity, underscoring the imperative for refined patient stratification. Classical biomarkers such as PD-L1 expression, tumor mutational burden (TMB), mismatch-repair status, Epstein–Barr virus (EBV) positivity and circulating tumor DNA (ctDNA) all demonstrate predictive value but remain constrained by spatial heterogeneity and temporal dynamics. Consequently, we highlight emerging biomarkers that integrate metabolic, epigenetic and cell-death signatures, providing a roadmap for precision immunotherapy and continuous optimization of GC treatment algorithms.

In solid tumors, hypoxia-inducible factor (HIF) is upregulated in various cell types within the tumor microenvironment (TME) due to hypoxia. In tumor cells, HIF signaling acts as a primary driver: it triggers metabolic reprogramming toward the Warburg effect and upregulates various angiogenic factors to support adaptation to hypoxia. Meanwhile, it promotes malignant progression by regulating cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. In immune cells, HIF signaling precisely regulates the abundance and function of various immune cell subsets, thereby establishing an immunosuppressive microenvironment that enables tumor cells to evade immune surveillance. Ultimately, HIF signaling in different cell types acts in concert and constitutes a key factor that attenuates the therapeutic efficacy of immune checkpoint inhibitors (ICIs). Over the decades of the development of HIF inhibitors, the antitumor effects of a large number of these agents have been validated in preclinical studies, with some having entered clinical trials or obtained clinical approval. Although only a small subset of HIF inhibitors has been verified to exert synergistic effects when combined with ICIs in experimental settings, it is undeniable that HIF inhibitors have emerged as a crucial "reserve force" for overcoming ICI resistance. Their potential in reshaping the immune microenvironment and enhancing the efficacy of ICIs provides a new direction for the immunotherapy of hypoxic solid tumors.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder that significantly reduces patients' quality of life. However, current animal models have limitations in replicating the complex pathophysiology of IBS. In this study, we successfully developed a mouse model by mating intestinal epithelium-specific Cre tool mice with chemically modified human muscarinic acetylcholine receptor 3 (hCHRM3) mice, resulting in specific expression of the hCHRM3 in the intestinal epithelial cells. Activation of the hCHRM3 with clozapine-N-oxide (CNO) mimicked IBS attacks. The model mice exhibited typical IBS symptoms such as diarrhea, pain, and visceral hypersensitivity, along with pathological changes like intestinal edema and inflammatory cell infiltration, and disruption of the intestinal mucosal barrier. RNA sequencing revealed significant differentially expressed genes between the model and control groups, with KEGG and GO enrichment analyses indicating significant enrichment of immune and inflammation-related pathways. Additionally, the model mice showed increased levels of short-chain fatty acids and imbalances in the diversity and composition of the gut microbiota. This new IBS mouse model effectively simulates the symptoms and pathological processes of human IBS, providing a powerful tool for in-depth research into the pathogenesis of IBS and the development of therapeutic strategies.

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal malignancy, presenting significant challenges in clinical diagnosis and treatment. The chemokine C-C motif ligand 5 (CCL5) plays a pivotal role in HCC pathogenesis. While traditionally viewed primarily as a mediator of immune cell chemotaxis and migration, recent evidence demonstrates that CCL5 directly influences tumor cells, regulating malignant behaviors such as proliferation and invasion. Furthermore, CCL5 recruits diverse immune cells, including immunosuppressive populations, to the tumor microenvironment (TME), remodeling the TME and exerting context-dependent effects that can either promote immune evasion or enhance anti-tumor immunity. This article reviews advances in understanding the mechanisms of CCL5 in HCC and discusses the translational potential of targeting CCL5 for HCC therapy.

Acute pancreatitis (AP), characterized by pancreatic autodigestion and systemic inflammation, remains a life-threatening condition with a high mortality rate in severe cases. Cholinergic signaling through muscarinic receptors (mAChRs) regulates pancreatic exocrine secretion, yet the role of chronic cholinergic hyperactivation in AP progression is poorly understood. Protease inhibitors like VR23, a potent trypsin-selective compound, hold therapeutic potential but lack evaluation in AP models. This study aimed to investigate the effects of prolonged cholinergic stimulation on AP severity and evaluate the efficacy of VR23 in mitigating pancreatic injury. Male C57BL/6 mice were pretreated with intragastric carbachol (5 mg/kg, twice daily for 7 days) to mimic chronic cholinergic hyperactivation, followed by intraperitoneal caerulein (100 μg/kg, 10 hourly doses) to induce AP. VR23 (30 mg/kg) was administered intraperitoneally 12 h and 3 h before caerulein. Pancreatic injury was assessed via histopathology (HE-staining), serum amylase/lipase activity, western blot (trypsin/amylase), RT-qPCR (TNF-α, IL-1β, IL-6, IL-18), MPO immunohistochemistry (neutrophil infiltration), HMGB1 immunohistochemistry (necrosis) and TUNEL staining (apoptosis). Long-term carbachol stimulation induced acinar cell hypertrophy and elevated intracellular trypsin synthesis, exacerbating caerulein-induced AP with increased pancreas-to-body weight ratio, histopathological scores, serum amylase/lipase, and pro-inflammatory cytokines. Neutrophil infiltration and apoptosis were significantly amplified. VR23 pretreatment attenuated pancreatic injury, reducing histopathological scores, serum enzymes, inflammatory cytokines, neutrophil infiltration, and apoptosis. Long-term chronic cholinergic stimulation exacerbates AP by enhancing trypsin synthesis, inflammatory responses, and apoptosis. VR23 demonstrates therapeutic efficacy by inhibiting protease activity and modulating inflammation, highlighting its potential as a targeted treatment for AP.

Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury. After injury, Schwann cells produce an inflammatory response and secrete various chemokines, inflammatory factors, and some other cytokines to promote the recruitment and M2 polarization of blood-derived macrophages, enhancing their phagocytotic ability, and thus play an important role in promoting nerve regeneration. Macrophages have also been found to promote vascular regeneration after injury, promote the migration and proliferation of Schwann cells along blood vessels, and facilitate myelination and axon regeneration. Therefore, there is a close interaction between Schwann cells and macrophages during peripheral nerve regeneration, but this has not been systematically summarized. In this review, the mechanisms of action of Schwann cells and macrophages in each other's migration and phenotypic transformation are reviewed from the perspective of each other, to provide directions for research on accelerating nerve injury repair.

Neurological disorders are increasing worldwide, imposing a major social and economic burden. Therefore, there is an urgent need to explore effective treatment methods to alleviate neurological disorders. Celastrol, derived from the traditional Chinese medicine Tripterygium wilfordii Hook. f., has been shown in multiple studies to exhibit promising neuroprotective effects in neurodegenerative, including Parkinson's disease, Alzheimer's disease, and spinal cord injury. The targets or pathways through which celastrol exerts its neuroprotective effects are diverse. This paper primarily focuses on in vivo animal models (such as Parkinson's disease mouse models, Alzheimer's disease mouse models) and in vitro cell models (such as neuronal cell lines, primary cultured neurons) experiments to comprehensively summarize the molecular mechanisms underlying celastrol's neuroprotective effects. Celastrol exerts its neuroprotective effects through pathways such as reducing inflammation, activating the autophagy-lysosome pathway, and inhibiting ferroptosis. Additionally, we discuss the current challenges faced by celastrol and potential strategies to address them. Collectively, these findings highlight celastrol as a promising therapeutic candidate, although further pharmacokinetic optimization and clinical validation are essential.

Accumulating evidence suggested that both gut microbiome and sex play a critical role in the efficacy of immune checkpoint blockade therapy. Considering the reciprocal relationship between sex hormones and gut microbiome, the sex hormone-gut microbiome axis may participate in the regulation of the response to immune checkpoint inhibitors (ICIs). In this review, it was attempted to summarize the current knowledge about the influences of both sex and gut microbiome on the antitumor efficacy of ICIs and describe the interaction between sex hormones and gut microbiome. Accordingly, this review discussed the potential of enhancing the antitumor efficacy of ICIs through regulating the levels of sex hormones through manipulation of gut microbiome. Collectively, this review provided reliable evidence concerning the role of the sex hormone-gut microbiome axis in tumor immunotherapy.

The CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6), which binds to the programmed death ligand 1 (PD-L1) and stabilizes the expression of PD-L1 on the cell surface, has been recently discovered as a novel regulator of PD-L1 expression in cancer. PD-L1 is an immune checkpoint inhibitory molecule that can mediate the immune escape of tumor cells in various tumors and has been studied intensively in recent years. In 2017, two articles simultaneously reported that CMTM6 can stabilize the expression of PD-L1 on the plasma membrane and prevent PD-L1 from being degraded by lysosomes; therefore, CMTM6 may play an important role in tumor cell immune escape and immunosuppression. At present, there are few studies on the relationship between the expression of CMTM6 and PD-L1 in different tumors and diseases. These studies together suggested that CMTM6 may be a potential novel immunotherapy target. In this review, we briefly describe the latest research progresses of CMTM6 in various cancers and other diseases.

Sciatic nerve injury affects quality of life. Many immune cells and inflammatory cytokines have been reported to be involved in sciatic nerve injury, but little is known about the ligands and receptors that trigger inflammatory responses. By using a modified sciatic nerve clamp injury method, we found that the recruitment of Schwann cells and the inflammatory response were enhanced after sciatic nerve injury. Toll-like receptor 4 (TLR4), one of the major members of the TLR family, is highly expressed in Schwann cells. Under certain conditions, myeloid differentiation protein 2 (MD2) binds to TLR4 on the membrane and plays important roles in the inflammatory response. The reductions in the recruitment of Schwann cells and the inflammatory response induced by the blockade of TLR4 or MD2 suggest that TLR4 and MD2 are involved in sciatic nerve injury. What are the endogenous signals that activate the inflammatory response? A large number of free saturated fatty acids (SFAs) are released from Schwann cells, adipocytes and the blood after sciatic nerve injury. Liang et al reported that Schwann cells can be stimulated by palmitic acid (PA). Here, we found that the expression and secretion of TNF-α and IL-6 were enhanced by PA treatment. Moreover, PA activated TLR4 signalling pathway-related proteins and stimulated a strong association between TLR4 and MD2. Blocking TLR4 or MD2 reversed the PA-induced inflammatory response and TLR4 downstream signalling pathway. Thus, we speculated that SFAs act as endogenous ligands that activate TLR4/MD2, thus triggering Schwann cell inflammation during sciatic nerve injury.

The activation of the inflammasome plays an important role in the central nervous system. However, only a few studies have investigated the effects of inflammasome activation in the peripheral nerve, especially in the sciatic nerve, and the mechanism of this activation remains elusive. Moreover, how interleukin-1 beta (IL-1β) is produced after sciatic nerve injury is also unknown. In our study, we aimed to investigate whether the nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) inflammasome is activated after sciatic nerve injury and to explore its role in sciatic nerve injury. The results of immunoblotting and immunofluorescence microscopy indicate that the NLRP3 inflammasome was activated after sciatic nerve injury in wild-type (WT) mice, as demonstrated by upregulated inflammasome-related components, e.g., NLRP3, procaspase-1 and ASC. Furthermore, upregulated inflammasome-related components cis-cleavage precursor IL-1β (proIL-1β) and precursor interleukin-18 (proIL-18) to IL-1β and IL-18, contributing to the inflammatory response. Consequently, the inflammatory response after sciatic nerve injury in NLRP3 knockout (NLRP3-KO) mice was less severe than that in WT mice. Moreover, NLRP3-KO mice exhibited an increased sciatic functional index (SFI), which was determined by footprint analysis, suggesting that NLRP3 deficiency is beneficial to sciatic nerve recovery after injury. Therefore, our results indicate that NLRP3 is involved in the recovery from sciatic nerve injury and mediates the production of inflammatory factors, such as IL-1β, after sciatic nerve injury.

Acute liver injury is a common pathological basis for a variety of acute liver diseases in the clinic, which can eventually lead to liver fibrosis and even liver failure. In this study, we found that T cell Ig and mucin domain protein 3 (Tim-3) and TLR4 receptors play important roles in CCl4-induced acute liver injury. Tim-3 is a negative regulator that is expressed by T cells and macrophages. Using antibodies against Tim-3 (anti-Tim-3 Ab), we studied the Tim-3 signal in an animal model of acute liver injury and found that a large number of inflammatory factors were upregulated. In vitro experimental data shown that anti-Tim-3 Ab treatment increased interferon-ɣ production by concanavalin A (ConA)-stimulated spleen T cells, and we found that the expression level of interleukin (IL)-6 was increased in a macrophage/spleen T cell coculture system, while administration of galectin-9 (Gal-9, a Tim-3 ligand) reduced the IL-6 production. This indicates the importance of the Tim-3/Gal-9 signalling pathway in maintaining hepatic homeostasis. The Tim-3 signalling pathway inhibits TLR4-mediated NF-κB activity, and an anti-Tim-3 Ab does not affect the liver injury in TLR4-deficient mice. Regulation between Tim-3 and TLR4 determines the severity of liver damage. The negative regulation of Tim-3 reflects the protective mechanisms of patients with impaired liver function, and these results provide important information about innate and adaptive responses in the regulation of liver damage. This finding is potentially important for the study of early liver injury.

Recently, the link between inflammation and cancer has been targeted for the prevention or treatment of malignant tumours. We aimed to investigate the relationship between Th17 cells and CXCL1 in breast cancer and the biological effects of CXCL1 on breast cancer. In vivo, the Th17 cell frequency in the peripheral blood was determined by flow cytometry. Secretion of IL-17 and CXCL1 in the blood serum was determined by enzyme-linked immunosorbent assay (ELISA). Expression of IL-17A and CXCL1 mRNA was determined by qRT-PCR. In vitro, the effects of Th17/CXCL1 during breast cancer were assessed in the human breast cancer cell lines MCF-7 and MDA-MB-231. Cell proliferation was measured using the CCK8 assay. Cell invasion and migration ability were assessed using a transwell cell invasion and wound- healing assay. In vivo, Th17 cells and CXCL1 were increased in breast cancer patients. Moreover, their changes were correlated in breast cancer cells. Th17 cells upregulate the production of CXCL1 during breast cancer progression. CXCL1, which is produced by breast cancer cells, can promote cancer growth and development, and may also point to a specific histogenetic pathway.

Objective: The aim of this study is to distinguish whether Toll-like receptor 4 (TLR4) signaling is included in Wallerian degeneration (WD) and nerve regeneration or not after peripheral nerve injury. Methods: The rats were assigned into four groups randomly: sham group (n = 10), control group (n = 10), model group (n = 20), and treatment group (n = 20). The rats were treated with TAK-242 (0.15 mg/kg) or saline. TAK-242, a small molecular that inhibit TLR4 signaling was first given to rats intravenously 1 h before nerve injury and followed by daily injections for 7 consecutive days. Animals were sacrificed 1.5 h, 24 h, 3 d, 4 d, or 7 d after surgery. Real-time quantitative PCR (qRT-PCR) was adopted to test dynamic mRNA expressions of TIR-domain-containing adaptor inducing interferon-beta (TRIF), interleukin-1 (IL-1 beta) and monocyte chemoattractant protein-1 (MCP-1). Immunofluorescence (IF) was used to test the expression of CD68(+) macrophages and iba1(+) Schwann cells in sciatic nerves. Luxol Fast Blue (LFB) staining was applied to test sciatic nerves myelin, and Haematoxylin-eosin (HE) staining was conducted in sciatic nerves tissue to observe the pathological variations. Immunohistochemistry (IHC) was applied to test the form of TRIF and growth associated protein-43 (GAP-43) in sciatic nerve, and sciatic function index (SFI) was applied to assess the recovery of motor function in rats. Results: The expressions of TRIF, IL-1 beta, MCP-1 and recruitments of Schwann cells and macrophages in sciatic nerve of rats were decreased significantly in treatment group compared with model group after peripheral nerve injury. Myelin clearance and axonal regeneration were delayed in treatment group compared with model group. HE staining also indicated a poor organization of repair site in treatment group in distal stump. Finally, the SFI scores of treatment group at each time point (20, 30, and 40 d post-injury) was lower than that of model group. Conclusions: TLR4 signaling might affect myelin phagocytosis and nerve regeneration during WD in rat after peripheral nerve injury via regulating the innate immune response.

OBJECTIVE:To investigate the changes of CD4(+)CD25(+)Foxp3(+) T cells (Treg), CD4(+)IL-17(+) T cells (Th17) and their related cytokines in patients with chronic hepatitis B (CHB), and explore the role of Th17/Treg balance in the progression of CHB.METHODS:Thirty-five patients with light-to-moderate chronic hepatitis B (CHB-LM), 25 patients with chronic severe hepatitis B (CSHB) and 21 healthy controls were enrolled. The frequencies of Th17 and Treg in peripheral blood were measured by flow cytometry (FCM), and the levels of IL-17, IL-23, IL-10 and TGF-β1 in sera were analyzed by double-antibody ELISA.RESULTS:Compared with health controls, the frequency of Th17, Treg and their cytokines (IL-17, IL-23, IL-10 and TGF-β1) increased significantly in CHB patients. Furthermore, the ratio of Th17/Tregs increased markedly in CHB patients compared with health controls, and it was significantly higher in CHB-LM than in CSHB.CONCLUSION:The imbalance of Th17/Treg plays an important role in the progression of CHB, and the ratio of Th17/Treg has a certain forecast value for finding the early development of the disease.