Hongzhen Chen , Dapeng Yang , Yirui Shi , Haolin Wu , Huiming Zhu , Tingting Jiang , Shu Liu , Dandan Wang
{"title":"The effect of tocilizumab treatment for skin fibrosis by inhibiting CD38+ macrophages in systemic sclerosis","authors":"Hongzhen Chen , Dapeng Yang , Yirui Shi , Haolin Wu , Huiming Zhu , Tingting Jiang , Shu Liu , Dandan Wang","doi":"10.1016/j.cellimm.2024.104914","DOIUrl":"10.1016/j.cellimm.2024.104914","url":null,"abstract":"<div><h3>Background</h3><div>Dermal and pulmonary fibrosis are the main clinical symptoms of systemic scleroderma (SSc), for which there are no effective therapeutic agents. Tocilizumab is thought to improve the symptoms of fibrosis, but the effect of tocilizumab on dermal fibrosis has not been explored. This study aims to investigate the therapeutic effect of tocilizumab on skin fibrosis by inhibiting CD38<sup>+</sup> macrophages in the bleomycin-induced SSc mice model.</div></div><div><h3>Methods</h3><div>The 8-week-old BALB/c mice were randomly divided into three groups: control group (PBS group), model group (BLM group), and tocilizumab group (TCZ group). The mRNA expression of VIMENTIN, TIMP1, and COL1A1 was measured by qPCR. Western blot was used to detect the protein expression of α-SMA, TGF-β, and COL1A1 in skin tissues. The expression of CD38<sup>+</sup> macrophages in the BLM-induced fibrosis mouse model was verified by flow cytometry and immunofluorescence.</div></div><div><h3>Results</h3><div>In comparison to the PBS control group, mice in the BLM group showed skin fibrosis, edema, thickness, and collagen deposition. The percentage of macrophages in the skin, peripheral blood, and spleen was significantly increased in the BLM group, and the percentage of CD38<sup>+</sup> macrophages increased in the skin and peripheral blood but decreased in the spleen. After co-cultured with macrophages, L929 fibroblasts differentiated into myofibroblasts, with increased mRNA expression of COL1A1, COL3A, TGF-β, and Fibronectin. Furthermore, after being stimulated by LPS, RAW264.7 cells showed increased expression of IL-6 and CD38. The mRNA levels of COL1A1, COL1A2, COL3A, TGF-β, and Fibronectin in L929 fibroblasts were markedly increased when co-cultured with LPS-stimulated RAW264.7 cells. Tocilizumab treatment reduced dermal thickness and collagen deposition induced by BLM. Furthermore, the percentage of total macrophages and CD38<sup>+</sup> macrophages in the skin and peripheral blood significantly decreased after tocilizumab treatment.</div></div><div><h3>Conclusion</h3><div>This study revealed that tocilizumab improved skin fibrosis in the SSc mice model, which was mediated by inhibiting skin and peripheral CD38<sup>+</sup> macrophages.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"408 ","pages":"Article 104914"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuta Sakamoto , Masatoshi Niwa , Ken Muramatsu , Satoshi Shimo
{"title":"Effect of high-fat diet on IgA+ cells and BAFF/APRIL in small intestinal villous lamina propria of mice","authors":"Yuta Sakamoto , Masatoshi Niwa , Ken Muramatsu , Satoshi Shimo","doi":"10.1016/j.cellimm.2024.104911","DOIUrl":"10.1016/j.cellimm.2024.104911","url":null,"abstract":"<div><div>Obesity exacerbates susceptibility to infectious diseases. We investigated the effects of a high-fat diet (HFD) on intestinal immunity, particularly immunoglobulin (Ig)A-producing cells, B-cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) localization. Mice (4- to 20-weeks old) were fed HFD or standard chow diet, and their jejunum and ileum were fixed using the <em>in vivo</em> cryotechnique. Immunohistochemistry was performed for IgA, BAFF, and APRIL. In the HFD group, IgA<sup>+</sup>, IgA<sup>+</sup>CD22<sup>+</sup> (<em>p</em> < 0.001), and IgA<sup>+</sup>CD138<sup>−</sup> (<em>p</em> = 0.007) cell counts were diminished in the middle sections of the lamina propria of jejunal villi, and BAFF levels were significantly reduced in jejunal villi. The HFD effects on IgA<sup>+</sup> cell distribution seem to be confined to jejunal villi, hinting at localized vulnerabilities in intestinal immunity during obesity. Moreover, in the HFD group, IgA<sup>+</sup> B-cell counts were reduced in the middle jejunum, indicating inhibition of the IgA<sup>+</sup> B-cells through a T-cell-independent pathway.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104911"},"PeriodicalIF":3.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IL-17 family members exert an autocrine pro-inflammatory loop in CF respiratory epithelial cells ex vivo","authors":"Caterina Allegretta , Enza Montemitro , Fabiana Ciciriello , Maria Teresa Altieri , Giuseppe Sabbioni , Giulia Breveglieri , Monica Borgatti , Giulio Cabrini , Onofrio Laselva","doi":"10.1016/j.cellimm.2025.104926","DOIUrl":"10.1016/j.cellimm.2025.104926","url":null,"abstract":"<div><h3>Background</h3><div>Lungs of people with Cystic Fibrosis (pwCF) are characterized by chronic inflammation and infection with <em>P. aeruginosa</em>. High levels of IL-17 A and F have been observed in sputum of pwCF and the interleukin-17(IL-17) family (A-to-F) has been suggested to play a key role in CF pulmonary disease.</div></div><div><h3>Methods</h3><div>We measured mRNA levels of IL-17 receptors (IL-17R) by RT-qPCR in CF bronchial epithelial (CFBE) cultured cells upon infection with <em>P. aeruginosa</em> PAO1 strain or clinical exoproducts (EXO) isolated from pwCF. We measured IL-17 mRNA expression by RT-qPCR and the release of cytokines by ELISA and Bioplex from CF primary nasal epithelial (HNE) cultured cells.</div></div><div><h3>Results</h3><div>Infection of CFBE cells with PAO1 or EXO isolated from 15 pwCF significantly increased mRNA expression of all IL-17R, except IL-17RD. Infection of HNE cells with EXO isolated from the correspondent donor significantly increased the mRNA levels of all the IL-17 cytokines and receptors, except for IL-17D and IL-17RD, and the release of the cytokines IL-17 A, IL-17B, IL-17C, IL-17E and IL-17F. HNE exposed to IL-17 A and F were induced to release pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), neutrophil chemokines (IL-8, G-CSF) and cytokines known to be involved in chloride and bicarbonate secretion, together with mucin upregulation (IL-4, IL-13).</div></div><div><h3>Conclusion</h3><div>These results highlight a wider expression of IL-17 family member in respiratory epithelial cells, which can play a role as an autocrine inflammatory amplification loop in CF airways. These in-vitro studies using patient-derived cultures underline the relevant role of IL-17 family members in CF pulmonary immune response.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104926"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wan-Li Yang , Chao Yang , Nan Pang , Rui-Hua Yu , Kui-Yuan Tong , Feng Jiang
{"title":"The distinct characteristic of two peritoneal macrophage subsets in a mouse model of hepatocellular carcinoma presents a novel therapeutic strategy","authors":"Wan-Li Yang , Chao Yang , Nan Pang , Rui-Hua Yu , Kui-Yuan Tong , Feng Jiang","doi":"10.1016/j.cellimm.2025.104917","DOIUrl":"10.1016/j.cellimm.2025.104917","url":null,"abstract":"<div><div>The peritoneal cavity (PerC) is a discrete anatomical compartment housing diverse peritoneal macrophage subpopulations. Nonetheless, there exists a paucity of knowledge concerning the distinct functions of these subpopulations in the context of hepatocellular carcinoma (HCC) and their evolution throughout tumor advancement. This investigation seeks to analyze the characteristics of two principal peritoneal macrophage subpopulations, specifically large peritoneal macrophage (LPM) and small peritoneal macrophage (SPM), in the context of HCC. The results of our research indicate a significant decrease in the proportion of LPM during the progression of HCC, accompanied by an increase in the quantity of SPM. Furthermore, SPM found in ascites exhibited a macrophage phenotype that supports tumor growth in HCC. Importantly, the dynamic decrease of LPM in murine models following lipopolysaccharide (LPS) stimulation led to a decrease in survival rate, highlighting the critical role of the altered LPM to SPM ratio in HCC survival. By employing clodronate liposomes (CL) to deplete peritoneal macrophage in murine models, followed by the adoptive transfer of LPM, we effectively prolonged the survival of HCC and attenuated tumor progression. Our results suggest that a decrease in the LPM to SPM ratio correlates with increased mortality in the HCC model. On the contrary, the maintenance of a high ratio of LPM to SPM has shown a positive effect on HCC survival. These findings have enhanced our understanding of the complex interaction between different subpopulations of peritoneal macrophage in the development of HCC. Furthermore, these results have important implications for the development of novel therapeutic strategies.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104917"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao'e Fan , Manhong Xu , Zhengmin Wang , Xiaoyan Sun , Yan Fan , Jiaqi Chen , Junpeng Hao , Ranran Wang , Wei Jia
{"title":"Arctiin suppress Th17 cells response and ameliorates experimental autoimmune uveitis through JAK/STAT signaling","authors":"Xiao'e Fan , Manhong Xu , Zhengmin Wang , Xiaoyan Sun , Yan Fan , Jiaqi Chen , Junpeng Hao , Ranran Wang , Wei Jia","doi":"10.1016/j.cellimm.2025.104927","DOIUrl":"10.1016/j.cellimm.2025.104927","url":null,"abstract":"<div><div>Conventional treatments for autoimmune uveitis, such as corticosteroids and systemic immunosuppressants, often result in adverse side effects, prompting the need for therapies targeting specific molecular pathways. This study investigates the effects of Arctiin, known for its diverse biological properties, on experimental autoimmune uveitis (EAU) through its action on Th17 cells and the JAK/STAT signaling pathway. Our findings reveal that Arctiin significantly alleviates EAU by reducing clinical scores, inflammatory cell infiltration, and levels of inflammatory cytokines like IL-17 and TNF-α in the eye. Arctiin achieves this by activating adiponectin receptor 1 (AdipoR1), which modulates the JAK/STAT pathway, thereby inhibiting Th17 cell differentiation and cytokine secretion. Additionally, Arctiin effectively suppresses IRBP-specific Th17 cell activation in cervical lymph nodes, further mitigating retinal inflammation and tissue damage. These results underscore Arctiin's potential as a therapeutic agent for uveitis and other autoimmune inflammatory disorders through the modulation of the AdipoR1/JAK/STAT pathway in Th17 cells.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104927"},"PeriodicalIF":3.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Fang , Jin Wang , Xinyue Zhao, Yaping Yang, Yujia Xiao
{"title":"KLHDC8A knockdown in normal ovarian epithelial cells promoted the polarization of pro-tumoral macrophages via the C5a/C5aR/p65 NFκB signaling pathway","authors":"Jie Fang , Jin Wang , Xinyue Zhao, Yaping Yang, Yujia Xiao","doi":"10.1016/j.cellimm.2024.104913","DOIUrl":"10.1016/j.cellimm.2024.104913","url":null,"abstract":"<div><h3>Aims</h3><div>Tumor-associated macrophages (TAM) is related to Ovarian cancer (OC) pathogenesis, but the exact mechanism remains unclear. This study investigated the expression of Kelch Domain Containing 8 A (KLHDC8A) in OC and the mechanism associated with TAM.</div></div><div><h3>Main methods</h3><div>Bioinformatics analysis of differential expression genes between normal and OC tissues were analyzed based on the Tumor Genome Atlas (TCGA) databases. KLHDC8A mRNA expression was knocked down in normal epithelial cells (IOSE80), and then the effects of siKLHDC8A on the proliferation, invasion, migration and C5a secretion of IOSE80 cells were explored. THP1-derived macrophages were cultured with medium of NC-IOSE80 cells, siKLHDC8A-IOSE80 cells with or without C5aR antagonists.</div></div><div><h3>Key findings</h3><div>KLHDC8A was lowly expressed in OC and negatively correlated with the infiltration of tumor-promoting macrophages, contributing to the survival of OC patients. Furthermore, siKLHDC8A promotes the proliferation, invasion and migration of IOSE80 cells and leads to polarization of pro-tumoral macrophages, which can be rescued by C5aR antagonists.</div></div><div><h3>Significance</h3><div>Our results indicated that KLHDC8A knockdown could modulate the development of OC by affecting macrophage polarization to pro-tumoral type via the C5a/C5aR/p65 NFκB signaling pathway. It may play an essential role as the tumor suppressor genes in diagnosis and treatment of OC.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104913"},"PeriodicalIF":3.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eva M. Gossink , Paul J. Coffer , Alessandro Cutilli , Caroline A. Lindemans
{"title":"Immunomodulation by galectin-9: Distinct role in T cell populations, current therapeutic avenues and future potential","authors":"Eva M. Gossink , Paul J. Coffer , Alessandro Cutilli , Caroline A. Lindemans","doi":"10.1016/j.cellimm.2024.104890","DOIUrl":"10.1016/j.cellimm.2024.104890","url":null,"abstract":"<div><div>Galectins, glycan-binding proteins, have been identified as critical regulators of the immune system. Recently, Galectin-9 (Gal-9) has emerged as biomarker that correlates with disease severity in a range of inflammatory conditions. However, Gal-9 has highly different roles in the context of immunoregulation, with the potential to either stimulate or suppress the immune response. Neutralizing antibodies targeting Gal-9 have been developed and are in early test phase investigating their therapeutic potential in cancer. Despite ongoing research, the mechanisms behind Gal-9 action remain not fully understood, and extrapolating the implications of targeting this molecule from previous studies is challenging. Here, we examine the pleiotropic function of Gal-9 focusing on conventional T lymphocytes, providing a current overview of its immunostimulatory and immunosuppressive roles. In particular, we highlight that Gal-9 differentially regulates immune responses depending on the context. Considering this complexity, further investigation of Gal-9′s intricate biology is necessary to define therapeutic strategies in immune disorders and cancer treatment aimed at inducing or inhibiting Gal-9 signaling.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"407 ","pages":"Article 104890"},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Zhou , Zhonglin LV , Meichen Liu , Chunxiao Du , Lin Du , Zhenfang Gao , Ziying Jiang , Lanying Wang , Shuohua Wang , Meng Liang , Shun Xie , Yuxiang Li , Zhiding Wang , Ge Li , Yinxiang Wei , Gencheng Han
{"title":"Ubiquitination and degradation of MHC-II by Tim-3 inhibits antiviral immunity","authors":"Jie Zhou , Zhonglin LV , Meichen Liu , Chunxiao Du , Lin Du , Zhenfang Gao , Ziying Jiang , Lanying Wang , Shuohua Wang , Meng Liang , Shun Xie , Yuxiang Li , Zhiding Wang , Ge Li , Yinxiang Wei , Gencheng Han","doi":"10.1016/j.cellimm.2024.104889","DOIUrl":"10.1016/j.cellimm.2024.104889","url":null,"abstract":"<div><div>We previously reported that Tim-3, an immune checkpoint inhibitor, inhibits MHC-II expression, but the molecular mechanisms involved and the implications for antiviral immunity remain to be determined. Here, we found that during H1N1 infection, Tim-3 inhibits MHC-II expression in macrophages/microglia in vitro. Tim-3 interacts with MHC-II via its intracellular tail and induces proteasomal dependent degradation of MHC-II. In H1N1 infected macrophages/microglia, Tim-3 promotes the K48-linked ubiquitination of MHC-II via MARCH8, a ubiquitin E3 ligase that can be upregulated by Tim-3. In H1N1 infected mice, specific knockout of Tim-3 in macrophages leads to a decreased viral load, attenuates tissue damage and increases the survival rate. We have thus identified a novel mechanism by which Tim-3 mediates virus immune escape. Manipulating the Tim-3-MHC-II signaling pathway may provide a novel treatment for viral infections.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"407 ","pages":"Article 104889"},"PeriodicalIF":3.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peipei Chen , Yunshu Wang , Huaiping Tang , Zhuo Liu , Jing Wang , Tingting Wang , Yun Xu , Sen-Lin Ji
{"title":"Gastrodenol suppresses NLRP3/GSDMD mediated pyroptosis and ameliorates inflammatory diseases","authors":"Peipei Chen , Yunshu Wang , Huaiping Tang , Zhuo Liu , Jing Wang , Tingting Wang , Yun Xu , Sen-Lin Ji","doi":"10.1016/j.cellimm.2024.104888","DOIUrl":"10.1016/j.cellimm.2024.104888","url":null,"abstract":"<div><div>Pyroptosis, a form of inflammatory programmed cell death, plays a pivotal role in the pathogenesis of various diseases. This process is primarily mediated by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3). Gastrodenol (Bismuth tripotassium dicitrate, GAS) is a mineral compound which is used to treat duodenal and gastric ulcers associated with Helicobacter pylori. In this study, GAS was found to exhibit protective effects against classical pyroptosis in macrophages. Specifically, GAS effectively inhibits the activation of the NLRP3 inflammasome, Gasdermin D (GSDMD)-mediated pyroptosis, and the secretion of pro-inflammatory cytokines. Mechanistically, GAS inhibited NLRP3 oligomerization and reduced the oligomerization of adaptor protein apoptosis-associated speck like protein containing a caspase activation and recruitment domain (ASC) by directly binding to NLRP3. The interaction between GAS and NLRP3 is primarily mediated through hydrogen bonding and hydrophobic forces. Hydrogen bonds are formed with PHE-727, LEU-723, and ASP-700. Remarkably, GAS treatment attenuated pyroptosis-mediated inflammatory diseases, including experimental autoimmune encephalomyelitis (EAE), lipopolysaccharide (LPS)-induced septic, and monosodium urate (MSU)-induced peritonitis in mice. To conclude, this is the first report that discovered clinical old medicine GAS as a potent inhibitor of pyroptosis and propose a novel therapeutic strategy for the prevention and treatment of NLRP3-GSDMD mediated diseases.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104888"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu-e Guo , Jie Lv , Ping Shu , Xi Li , Ying Li , Junhong Guo , Guofang Chen , Yuping Li , Bo Lu , Wei Zhang , Yin Liu
{"title":"Drug screening identifies pyrrolidinedithiocarbamate ammonium ameliorating DSS-induced mouse ulcerative colitis via suppressing Th17 differentiation","authors":"Yu-e Guo , Jie Lv , Ping Shu , Xi Li , Ying Li , Junhong Guo , Guofang Chen , Yuping Li , Bo Lu , Wei Zhang , Yin Liu","doi":"10.1016/j.cellimm.2024.104887","DOIUrl":"10.1016/j.cellimm.2024.104887","url":null,"abstract":"<div><div>T helper 17 (Th17) cells play crucial roles in various autoimmune diseases, including ulcerative colitis (UC), which is characterized by widespread inflammation in the mucosa of the colon and rectum. To identify small-molecule compounds capable of inhibiting CD4<sup>+</sup> T cell differentiation into Th17 cells, we established a screening system. Through drug screening, we found that pyrrolidinedithiocarbamate ammonium (PDTC) effectively inhibits Th17 differentiation. In a dextran sulfate sodium (DSS)-induced UC mouse model, administration of PDTC significantly ameliorated colitis. PDTC treatment decreased the production of proinflammatory mediators and inhibited the proportion of Th17 cells in colitis-afflicted mice by suppressing NF-κB activation. These findings showed that PDTC can alleviate colitis by inhibiting NF-κB activation. The therapeutic effects of PDTC observed in a mouse model of UC provided a rationale for its application in clinical settings.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104887"},"PeriodicalIF":3.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}