Mannose-binding lectin-associated serine protease 2(MASP-2) is a member of serine protease family and plays a crucial role in activating the complement lectin pathway. When mannose residues on the surface of a pathogen are recognized by mannose-binding lectins (MBL) or fibrinogen collagen (FCN), MASP-2 is activated. This activation then triggers the cleavage of C4 and C2 to form C3 convertase, thereby initiating the lectin pathway of the complement system. Numerous studies have demonstrated that MASP-2 gene polymorphisms and serum levels are closely related with various diseases, including tumors, infectious diseases, autoimmune diseases and so on. In this review, we summarize the relationships between MASP-2 and tumors, infectious diseases, autoimmune diseases. We aim to provide a theoretical basis for the early diagnosis, prognosis evaluation and clinical treatment of various diseases.
Humans ; Mannose-Binding Protein-Associated Serine Proteases/metabolism* ; Neoplasms/metabolism* ; Autoimmune Diseases/genetics* ; Animals ; Polymorphism, Genetic ; Communicable Diseases/genetics*

OBJECTIVE: To investigate the action mechanism of formononetin (FN) in regulating T helper type 1 (Th1) cell differentiation and macrophage polarization through JAK/STAT signaling pathways in a mouse model of experimental autoimmune prostatitis (EAP). METHODS: Forty non-obese diabetic (NOD) male mice were randomly divided into four groups: normal control, EAP model control, low-dose FN (LFN, 50 mg/kg) and high-dose FN (HFN, 100 mg/kg). The EAP model was established in the latter three groups by subcutaneous injection of prostate antigens (PAgs) combined with complete Freund's adjuvant (CFA). After modeling, the mice in the LFN and HFN groups were treated intragastrically with FN at 50 and 100 mg/kg/d, respectively, and those in the normal and model controls groups with carboxymethylcellulose sodium (CMC-Na). At 42 days after treatment, all the animals were killed and relevant tissues collected for observation of the pathological changes in the prostate tissue by HE staining, detection of Th1 cell differentiation and macrophage polarization in the prostate by immunofluorescence double staining (labeling CD4 and interferon-γ ［IFN-γ］, inducible nitric oxide synthase ［iNOS］ and CD206), measurement of the ratio of Th1 cells/macrophages in the spleen by flow cytometry and the levels of IFN-γ and tumor necrosis factor-α (TNF-α) in the serum by ELISA, and determination of the expressions of phosphorylated (p)-Janus kinase (JAK)1, JAK1, p-JAK2, JAK2, p-signal transducer and activator of transcription (STAT1) in the prostate tissue by Western blot. RESULTS: Compared with the model controls, the mice treated with low- and high-dose FN exhibited more orderly arrangement of glandular epithelial cells, significantly reduced prostatic tissue inflammation scores (P<0.05), and decreased proportion of Th1 cells and expression of M1 macrophages (P<0.05), but increased expression of M2 macrophages in the prostate and spleen tissues (P<0.05). Besides, the levels of inflammatory cytokines IFN-γ (P<0.05) and TNF-α (P<0.05) in the serum of the mice in the LFN and HFN groups were remarkably reduced, and so were the ratios of p-JAK1/JAK1, p-JAK2/JAK2 and p-STAT1/STAT1 in the prostate tissues at the molecular level (P<0.05), indicating the therapeutic effect of FN on EAP by regulating JAK/STAT signaling pathways, promoting inflammation resolution, and restoring immune balance. CONCLUSION FN alleviates EAP by inhibiting JAK/STAT signaling pathways and regulating Th1 cell differentiation and macrophage polarization.
Animals ; Male ; Prostatitis/metabolism* ; Signal Transduction ; Mice ; Isoflavones/therapeutic use* ; Mice, Inbred NOD ; Autoimmune Diseases/metabolism* ; Macrophages ; Inflammation ; Th1 Cells ; Janus Kinases/metabolism* ; Cell Differentiation ; Disease Models, Animal ; STAT Transcription Factors/metabolism*

Two-pore-domain potassium channels (K2P) family is widely expressed in many human cell types and organs, which has important regulatory effect on physiological processes. K2P is sensitive to a variety of chemical and physical stimuli, and they have also been critically implicated in transmission of neural signal, ion homeostasis, cell development and death, and synaptic plasticity. Aberrant expression and dysfunction of K2P channels are involved in a range of diseases, including autoimmune, central nervous system, cardiovascular disease and others. The scope of this review is to give a detailed overview of the structure, function, pharmacological regulation, and related diseases of TREK-1 channels, a member of the K2P family.
Potassium Channels, Tandem Pore Domain/genetics* ; Humans ; Animals ; Cardiovascular Diseases/physiopathology* ; Autoimmune Diseases/metabolism* ; Central Nervous System Diseases/physiopathology*

Interleukin 24 (IL-24) is a member of the IL-10 cytokine family and is primarily synthesized by lymphocytes and activated monocytes. IL-24 exerts its immunological functions by interacting with membrane receptors or intracellular proteins, leading to the activation of Janus protein tyrosine kinase/signal transducer and activator of transcription (JAK/STAT), p38 mitogen-activated protein kinase (p38 MAPK), and endoplasmic reticulum stress pathways in target cells. This versatile cytokine has specific abilities to inhibit tumor proliferation and invasion, expedite wound healing, and contribute to cardiovascular protection. IL-24 is involved in the pathogenesis of various autoimmune and inflammatory disorders, presenting itself as a prospective therapeutic target for the treatment of such conditions. This article primarily delves into the role and mechanisms of IL-24 in physiological processes, aiming to provide novel insights and avenues for disease treatment.
Humans ; Animals ; Interleukins/physiology* ; Signal Transduction ; Endoplasmic Reticulum Stress ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Neoplasms/metabolism* ; Autoimmune Diseases/metabolism* ; Inflammation/immunology* ; STAT Transcription Factors/metabolism* ; Janus Kinases/metabolism*

As the central organ of metabolism, the liver plays a pivotal role in the regulation of the synthesis and metabolism of various nutrients within the body. Ferroptosis, as a newly discovered type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides, is involved in the physiological and pathological processes of a variety of acute and chronic liver diseases. Ferroptosis can accelerate the pathogenetic process of acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, and autoimmune hepatitis; while it can slower disease progression in advanced liver fibrosis and hepatocellular carcinoma. This suggests that targeted regulation of ferroptosis may impact the occurrence and development of various liver diseases. This article reviews the latest research progress of ferroptosis in various liver diseases, including acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, autoimmune hepatitis, liver fibrosis and hepatocellular carcinoma. It aims to provide insights for the prevention and treatment of acute and chronic liver diseases through targeting ferroptosis.
Humans ; Liver Diseases/etiology* ; Ferroptosis/physiology* ; Liver Neoplasms/pathology* ; Carcinoma, Hepatocellular/pathology* ; Liver Cirrhosis/etiology* ; Liver/pathology* ; Hepatitis, Autoimmune/metabolism* ; Liver Diseases, Alcoholic/metabolism*

OBJECTIVE: To explore the role of the CMTM2 gene in regulating testicular spermatogenesis in the mouse model of experimental autoimmune orchitis (EAO). METHODS: We constructed an EAO model in CMTM2 knockout and wild-type (WT) mice, studied the immunological reproductive phenotype and examined the number, morphology and activity of the sperm generated in the CMTM2 knockout mice. We assessed the infiltration of macrophages and lymphocytes in the testis tissue sections and Leydig cells, and determined the expression levels of CMTM2 in the homozygous knockout (KO), heterozygous and WT mice by RT-PCR, Western blot and Northern blot. RESULTS: Statistically significant differences were observed in the long testicular axis and the number of sperm generated between the KO and WT mice after reaching adulthood (P<0.05). The total numbers of macrophages and lymphocytes were markedly increased, while sperm motility and the percentage of morphologically normal sperm remarkably decreased in the testis of the KO mouse model compared with those in the WT mouse model of EAO. CONCLUSION The CMTM2 gene, as a regulator of spermatogenesis, is highly expressed in adult male mice and plays an important role in the maintenance of spermatogenesis. Moreover, decreased expression products of the CMTM2 gene may weaken spermatogenesis under chronic inflammation conditions.
Animals ; Male ; Mice ; Orchitis/genetics* ; Spermatogenesis/genetics* ; Disease Models, Animal ; Testis/metabolism* ; Autoimmune Diseases/genetics* ; Mice, Knockout ; MARVEL Domain-Containing Proteins/genetics*

OBJECTIVES: To study the clinical features of children with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). METHODS: A retrospective analysis was performed on the medical data of 34 children with GFAP-A who attended the Department of Neurology, Children's Hospital of Chongqing Medical University, from January 2020 to February 2022. The medical data included clinical manifestations, cerebrospinal fluid features, imaging examination results, treatment, and prognosis. RESULTS: The median age of onset was 8.4 (range 1.9-14.9) years for the 34 children with GFAP-A. The main clinical manifestations included headache (50%, 17/34), fever (47%, 16/34), visual impairment (47%, 16/34), and disturbance of consciousness (44%, 15/34). Abnormal cerebrospinal fluid results were observed in 19 children (56%, 19/34), among whom 8 children had positive autoantibody. The children with overlap syndrome had significantly higher recurrence rate and rate of use of immunosuppressant than those without overlap syndrome (P<0.05). About 77% (24/31) of the children had good response to immunotherapy, and only 1 child had poor prognosis. CONCLUSIONS Children with GFAP-A often have non-specific clinical symptoms and show good response to immunotherapy. Children with overlap syndrome have a high recurrence rate, and early application of immunosuppressants may help to prevent recurrence and alleviate symptoms.
Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Astrocytes/metabolism* ; Autoantibodies/metabolism* ; Glial Fibrillary Acidic Protein/metabolism* ; Prognosis ; Retrospective Studies ; Autoimmune Diseases/metabolism*

Autoimmune diseases are characterized by damage and dysfunction of multiple organs and various complications. Recently, new therapies for autoimmune diseases have been proposed extensively, and there are growing researches focusing on the immunomodulatory abilities of mesenchymal stem cells (MSCs). As a kind of small vesicles secreted by cells, exosomes can be released by MSCs and other cells. Being enriched with protein, mRNA, microRNA, lipids and other cell contents, exosomes participate in the transfer of substances and information between cells, and regulate the biological functions of recipient cells, which may be a potential mechanism of the immunomodulation abilities of MSCs. A growing number of studies have shown that the exosomes secreted by MSCs have similar or even better immunomodulation abilities than MSCs, and their roles in the treatment of several autoimmune diseases have been confirmed in animal models. In this review, we briefly summarize the effects of MSCs and the MSCs-derived exosomes on the immune system and immune cells, especially focusing on the research progress of MSCs-derived exosomes in autoimmune diseases in recent years.
Animals ; Autoimmune Diseases/therapy* ; Exosomes/metabolism* ; Immunomodulation ; Mesenchymal Stem Cells ; MicroRNAs/metabolism*

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence

The obstacle to successful remyelination in demyelinating diseases, such as multiple sclerosis, mainly lies in the inability of oligodendrocyte precursor cells (OPCs) to differentiate, since OPCs and oligodendrocyte-lineage cells that are unable to fully differentiate are found in the areas of demyelination. Thus, promoting the differentiation of OPCs is vital for the treatment of demyelinating diseases. Shikimic acid (SA) is mainly derived from star anise, and is reported to have anti-influenza, anti-oxidation, and anti-tumor effects. In the present study, we found that SA significantly promoted the differentiation of cultured rat OPCs without affecting their proliferation and apoptosis. In mice, SA exerted therapeutic effects on experimental autoimmune encephalomyelitis (EAE), such as alleviating clinical EAE scores, inhibiting inflammation, and reducing demyelination in the CNS. SA also promoted the differentiation of OPCs as well as their remyelination after lysolecithin-induced demyelination. Furthermore, we showed that the promotion effect of SA on OPC differentiation was associated with the up-regulation of phosphorylated mTOR. Taken together, our results demonstrated that SA could act as a potential drug candidate for the treatment of demyelinating diseases.
Animals ; Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Demyelinating Diseases ; prevention & control ; Encephalitis ; prevention & control ; Encephalomyelitis, Autoimmune, Experimental ; prevention & control ; Female ; Mice, Inbred C57BL ; Myelin Basic Protein ; metabolism ; Neuroprotective Agents ; administration & dosage ; Oligodendrocyte Precursor Cells ; drug effects ; metabolism ; Rats ; Remyelination ; drug effects ; Shikimic Acid ; administration & dosage ; TOR Serine-Threonine Kinases ; metabolism