Journal of immunology最新文献

{"title":"Inhibitory immunoreceptors CD300a and CD300lf cooperate to regulate mast cell activation.","authors":"Hanbin Lee, Chigusa Nakahashi-Oda, Wenxin Lyu, Mamoru Tanaka, Akiyoshi Rai, Yoichi Muramoto, Yaqiu Wang, Seiya Mizuno, Kazuko Shibuya, Akira Shibuya","doi":"10.1093/jimmun/vkae030","DOIUrl":"https://doi.org/10.1093/jimmun/vkae030","url":null,"abstract":"<p><p>Mast cells (MCs) play a central role in allergic immune responses. MC activation is regulated by several inhibitory immunoreceptors. The CD300 family members CD300a and CD300lf recognize phospholipid ligands and inhibit the FcεRI-mediated activating signal in MCs. While CD300a binds to phosphatidylserine (PS) to inhibit MCs activation, CD300lf function is less clear due to its ability to bind with ceramide and PS. Moreover, it also remains blurring whether CD300a and CD300lf function independently, cooperatively, or by interfering with each other in regulating MC activation. Using imaging and flow cytometric analyses of bone marrow-derived cultured MCs (BMMCs) from wild-type (WT), Cd300a-/-, Cd300lf-/-, and Cd300a-/-Cd300lf-/- mice, we show that CD300lf and CD300a colocalized with PS externalized to the outer leaflet of the plasma membrane with a polar formation upon activation, and CD300lf cooperates with CD300a to inhibit BMMCs activation. CD300lf also colocalized with extracellular ceramide in addition to the internal PS on the cell surface, which results in stronger inhibition of MC activation than CD300lf binding to PS alone. Similarly, although both Cd300a-/- and Cd300lf-/- mice showed decreased rectal temperatures compared with WT mice in the model of passive systemic anaphylaxis, Cd300a-/-Cd300lf-/- mice showed lower rectal temperature than either Cd300a-/- or Cd300lf-/- mice. Our results demonstrate the cooperativity of multiple inhibitory receptors expressed on MCs and their regulatory functions upon binding to respective ligands.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absence of c-Maf and IL-10 enables type I IFN enhancement of innate responses to LPS in alveolar macrophages.","authors":"Pamelia N Lim, Maritza M Cervantes, Linh K Pham, Sydney R Doherty, Ankita Tufts, Divya Dubey, Dat Mai, Alan Aderem, Alan H Diercks, Alissa C Rothchild","doi":"10.1093/jimmun/vkae029","DOIUrl":"10.1093/jimmun/vkae029","url":null,"abstract":"<p><p>Alveolar macrophages (AMs) are lung-resident myeloid cells and airway sentinels for inhaled pathogens and environmental particles. While AMs can be highly inflammatory in response to respiratory viruses, they do not mount proinflammatory responses to all airborne pathogens. For example, we previously showed that AMs fail to mount a robust proinflammatory response to Mycobacterium tuberculosis. Here, we address this discrepancy by investigating the capacity of murine AMs for direct innate immune sensing, using LPS as a model. Use of LPS-coated fluorescent beads enabled us to distinguish between directly exposed and bystander cells to measure transcriptional responses, by RNA-sequencing after cell sorting, and cytokine responses, by flow cytometry. We find that AMs have decreased proinflammatory responses to low-dose LPS compared to other macrophage types (bone marrow-derived macrophages, peritoneal macrophages), as measured by TNF, IL-6, Ifnb, and Ifit3. The reduced response to low-dose LPS correlates with minimal TLR4 and CD14 surface expression, despite sufficient internal expression of TLR4. We also find that AMs do not produce IL-10 in response to a variety of stimuli due to low expression of the transcription factor c-Maf, while exogenous c-Maf expression restores IL-10 production in AMs. Lastly, we show that lack of IL-10 enables type I IFN enhancement of AM responses to LPS. Overall, we demonstrate AMs have a cell-intrinsic hyporesponsiveness to LPS, which makes them uniquely tolerant to low-dose exposure. Regulation of AM innate responses by distinct CD14, c-Maf, and IL-10 expression patterns has important implications for both respiratory infections and environmental airborne exposures.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The aryl hydrocarbon receptor controls IFN-γ-induced immune checkpoints PD-L1 and IDO via the JAK/STAT pathway in lung adenocarcinoma.","authors":"Megan Snyder, Zhongyan Wang, Brian Lara, Jocelyn Fimbres, Táchira Pichardo, Sarah Mazzilli, Mohammed Muzamil Khan, Vinay K Duggineni, Stefano Monti, David H Sherr","doi":"10.1093/jimmun/vkae023","DOIUrl":"10.1093/jimmun/vkae023","url":null,"abstract":"<p><p>While immunotherapy has shown some efficacy in lung adenocarcinoma (LUAD) patients, many respond only partially or not at all. One limitation in improving outcomes is the lack of a complete understanding of immune checkpoint regulation. Here, we investigated a possible link between an environmental chemical receptor implicated in lung cancer and immune regulation, the AhR, a known but counterintuitive mediator of immunosuppression (interferon (IFN)-γ), and regulation of two immune checkpoints (PD-L1 and IDO). AhR gene-edited LUAD cell lines, a syngeneic LUAD mouse model, bulk and scRNA sequencing of LUADs and tumor-infiltrating T cells were used to map out a signaling pathway leading from IFN-γ through the AhR to JAK/STAT, PD-L1, IDO, and tumor-mediated immunosuppression. The data demonstrate that: (1) IFN-γ activation of the JAK/STAT pathway leading to PD-L1 and IDO1 up-regulation is mediated by the AhR in murine and human LUAD cells, (2) AhR-driven IDO1 induction results in the production of Kynurenine (Kyn), an AhR ligand, which likely mediates an AhR→IDO1→Kyn→AhR amplification loop, (3) transplantation of AhR-knockout LUAD cells results in long-term tumor immunity in most recipients. (4) The 23% of AhR-knockout tumors that do grow do so at a much slower pace than controls and exhibit higher densities of CD8+ T cells expressing markers of immunocompetence, increased activity, and increased cell-cell communication. The data definitively link the AhR to IFN-γ-induced JAK/STAT pathway and immune checkpoint-mediated immunosuppression and support the targeting of the AhR in the context of LUAD.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virulent African swine fever virus infection of porcine monocytes causes SLA I subversion due to loss of proper ER structure/function.","authors":"Luise Brose, Alexander Schäfer, Kati Franzke, Clemens Cammann, Ulrike Seifert, Gang Pei, Sandra Blome, Michael R Knittler, Ulrike Blohm","doi":"10.1093/jimmun/vkae063","DOIUrl":"https://doi.org/10.1093/jimmun/vkae063","url":null,"abstract":"<p><p>African swine fever virus (ASFV) is a large DNA virus of the Asfarviridae family that causes a fatal hemorrhagic disease in domestic swine and wild boar. Infections with moderately virulent strains predominantly result in a milder clinical course and lower lethality. As target cells of ASFV, monocytes play a crucial role in triggering T-cell-mediated immune defense and ASF pathogenesis. We compared the effect of the highly virulent \"Armenia2008\" (ASFV-A) virus strain with that of the naturally attenuated \"Estonia2014\" (ASFV-E) on cellular immune activation in vivo and on primary monocytes ex vivo. Specifically, we asked whether antigen presentation of porcine monocytes is impaired upon ASFV-A infection. ASFV-A-infected monocytes are characterized by lower levels of swine leukocyte antigen (SLA) class I on the cell surface than ASFV-E-infected and uninfected monocytes. Despite stable steady-state SLA I mRNA/protein levels and expression of critical components of the antigen processing machinery, a marked decrease in maturation and reduced surface transport of SLA I were observed in ASFV-A-infected monocytes. The intracellular maturation block of SLA I was accompanied by a loss of functional rough ER structures and a pronounced formation of ER-associated aggresomes. This unsolved cellular stress resulted in a shutdown of overall host cell protein translation, mitochondrial dysfunction, and caspase-3-mediated apoptosis. In contrast, no such cellular subversion phenomenon was found in ASFV-E-infected monocytes. Our findings suggest that in domestic pigs infected with highly virulent ASFV-A, sequential subversion events occur in infected monocytes, likely leading to compromised T-cell activation and impaired downstream responses against ASFV.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD3+ T-cell: CD14+ monocyte complexes are dynamic and increased with HIV and glucose intolerance.","authors":"Laventa M Obare, Joshua Simmons, Jared Oakes, Xiuqi Zhang, Cindy Nochowicz, Stephen Priest, Samuel S Bailin, Christian M Warren, Mona Mashayekhi, Heather K Beasley, Jianqiang Shao, Leslie M Meenderink, Quanhu Sheng, Joey Stolze, Rama Gangula, Tarek Absi, Yan Ru Su, Kit Neikirk, Abha Chopra, Curtis L Gabriel, Tecla Temu, Suman Pakala, Erin M Wilfong, Sara Gianella, Elizabeth J Phillips, David G Harrison, Antentor Hinton, Spyros A Kalams, Annet Kirabo, Simon A Mallal, John R Koethe, Celestine N Wanjalla","doi":"10.1093/jimmun/vkae054","DOIUrl":"10.1093/jimmun/vkae054","url":null,"abstract":"<p><p>Persistent systemic inflammation is associated with an elevated risk of cardiometabolic diseases. However, the characteristics of the innate and adaptive immune systems in individuals who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states. Using well-characterized clinical cohorts, including participants with controlled human immunodeficiency virus (HIV) as a model for chronic inflammation and increased immune cell interactions, we show that circulating CD14+ monocytes complexed to CD3+ T cells are dynamic, biologically relevant, and increased in individuals with diabetes after adjusting for confounding factors. The complexes form functional immune synapses with increased expression of proinflammatory cytokines and greater glucose utilization. Furthermore, in persons with HIV, the CD3+ T cell: CD14+ monocyte complexes had more HIV copies compared to matched CD14+ monocytes or CD4+ T cells alone. Our results demonstrate that circulating CD3+ T-cell: CD14+ monocyte pairs represent dynamic cellular interactions that may contribute to inflammation and cardiometabolic disease pathogenesis. CD3+ T-cell: CD14+ monocyte complexes may originate or be maintained, in part, by chronic viral infections. These findings provide a foundation for future studies investigating mechanisms linking T cell-monocyte cell-cell complexes to developing immune-mediated diseases, including HIV and diabetes.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-bet-expressing B cells promote atherosclerosis in apolipoprotein E-deficient mice.","authors":"James J Knox, Katalin Karolyi, James Monslow, Debra Cromley, Daniel J Rader, Ellen Puré, Michael P Cancro","doi":"10.1093/jimmun/vkae027","DOIUrl":"10.1093/jimmun/vkae027","url":null,"abstract":"<p><p>The humoral immune system influences the development of atherosclerosis, but the contributions of specific memory B cell subsets and IgG isotypes are poorly understood. We assessed the relationship between atherosclerosis and age-associated B cells (ABCs), a T-bet-expressing memory B cell subset that is enriched for IgG2c production and implicated in humoral autoimmunity. We found increased numbers of splenic CD11c+ ABCs in 6-mo-old, chow-fed Apoe-/- mice versus C57BL/6 control mice, which were exacerbated by high-fat diet. Deletion of T-bet in the B lineage in high-fat diet-fed Apoe-/- mice reduced aortic lesion area, and this correlated with decreased splenic CD11c+ B cells and reduced serum oxidized low-density lipoprotein-specific IgG2c. Our findings suggest that T-bet-expressing B cells are atherogenic agents in the Apoe-/- model and indicate that interventions to inhibit a T-bet-driven humoral response may improve atherosclerotic disease.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune memory in hepatitis E virus: a comparative study of natural infection and vaccination in a nursing home population.","authors":"Xiaoyue Wu, Daixi Jiang, Yuxia Du, Can Chen, Kexin Cao, Mengya Yang, Mengsha Chen, Wenkai Zhou, Jiaxing Qi, Dong Yan, Ziping Miao, Shigui Yang","doi":"10.1093/jimmun/vkae026","DOIUrl":"https://doi.org/10.1093/jimmun/vkae026","url":null,"abstract":"<p><p>Immune memory is crucial for preventing hepatitis E virus (HEV) infection. Our study aims to investigate immunological memory characteristics and differences between vaccination and natural HEV infection, taking into account that both can induce immune memory. We recruited 60 HEV-infected patients, 58 contingency HEV-vaccinated individuals and 4 controls from an outbreak of hepatitis E in a nursing home between June and August 2023. Multicolor flow cytometry, ELISA, and quantitative polymerase chain reaction (qPCR) were employed to detect memory T-cell expression profiles, HEV-specific antibodies and cytokine expression. We observed that the level of HEV-specific IgM in acute jaundiced hepatitis E patients was greater than that in non-jaundiced patients (8.37 ± 1.27 vs. 4.27 ± 0.81, P < 0.05). No significant differences were detected in the HEV-specific IgG and memory T cell expression profiles among the different severities of hepatitis E. The percentage of CD8+ TEM at 6 months after recovery was significantly greater than that in acute jaundice patients (1.60% ± 0.30% vs. 1.15% ± 0.35%, P < 0.05). Compared with natural infection, three-dose vaccination increased the level of HEV-specific IgG (14.97 ± 0.21 vs. 12.75 ± 0.37, P < 0.05), IL-7 and IL-15 (28.50 ± 3.82 vs. 23.32 ± 6.37, 608.60 ± 143.30 vs. 257.50 ± 69.87, P < 0.05). Natural infection could effectively establish immune memory. During convalescence, infection severity impacted only HEV-specific IgM, while HEV-specific IgG and memory T-cell expression profiles were not affected. Compared with natural infection, three-dose vaccination results in equal effective humoral immune memory and weaker cellular immune memory with minimal side effects.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UFL1 promotes survival and function of virtual memory CD8 T cells.","authors":"Brinda Bhatt, Kunal Kumar, Huidong Shi, Dhasarathan Ganesan, Francis Anazodo, Aravind Rathakrishnan, Huabin Zhu, Andrew Wanna, Chen Jiang, Tamilselvan Jayavelu, Vinata Bal Lokeshwar, Rafal Pacholczyk, David H Munn, Brian S Sheridan, Demetrius Moskophidis, Honglin Li, Nagendra Singh","doi":"10.1093/jimmun/vkae042","DOIUrl":"10.1093/jimmun/vkae042","url":null,"abstract":"<p><p>In naïve mice, a fraction of CD8 T cells displaying high affinity for self-MHC peptide complexes develop into virtual memory T (TVM) cells. Due to self-reactivity, TVM cells are exposed to persistent antigenic stimulation, a condition known to induce T cell exhaustion. However, TVM cells do not exhibit characteristics similar to exhausted CD8 T (TEX) cells. Here, we tested the role of the UFL1, E3 ligase of the ufmylation pathway in TVM cells. We show that UFL1 prevents the acquisition of epigenetic, transcriptional, and phenotypic changes in TVM cells that are similar to TEX cells and thus promote their survival and function. UFL1-deficient TVM cells failed to protect mice against Listeria infection. Epigenetic analysis showed higher BATF activity in UFL1-deficient TVM cells. Deletion of BATF and not PD1 decreased inhibitory molecules expression and restored the survival and function of UFL1-deficient TVM cells. Our findings demonstrate a key role of UFL1 in inhibiting the exhaustion of TVM cells and promoting their survival and function.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of sleep deprivation on monocyte subclasses and function.","authors":"Fatema Al-Rashed, Halemah Alsaeed, Nadeem Akhter, Haya Alabduljader, Fahd Al-Mulla, Rasheed Ahmad","doi":"10.1093/jimmun/vkae016","DOIUrl":"10.1093/jimmun/vkae016","url":null,"abstract":"<p><p>The relationship between sleep deprivation, obesity, and systemic inflammation is a critical area of investigation due to its significant impact on health. While it is established that poor sleep adversely affects obesity and metabolic syndromes, the specific mechanisms, particularly subclinical inflammation independent of obesity, remain unclear. This study investigates how sleep quality influences monocyte subclass distribution and its association with systemic inflammation across a spectrum of body mass index categories. In our cohort study, 237 healthy participants were categorized by body mass index. Participants' dietary intake, physical activity, and sleep patterns were objectively tracked through wearable ActiGraph GT3X accelerometer. The data showed that obese individuals had significantly lower sleep quality and higher chronic low-grade inflammation. Nonclassical monocytes increased significantly in obesity, correlating with reduced sleep quality and elevated proinflammatory cytokines. Although body mass index emerged as a significant factor in driving inflammation, mediation analyses further defined that sleep disruption independently contributes to inflammation, regardless of obesity status. Controlled sleep deprivation experiments confirmed these findings, demonstrating reversible increases in nonclassical monocytes expression. This study highlights the importance of sleep quality in regulating immune responses and inflammation in obesity, suggesting that improving sleep quality could reduce inflammation and improve health outcomes.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymic stromal lymphopoietin contributes to endometriotic lesion proliferation and disease-associated inflammation.","authors":"Stanimira Aleksieva, Harshavardhan Lingegowda, Danielle J Sisnett, Alison McCallion, Katherine B Zutautas, Dan Hoang Nguyet Vo, Timothy Childs, Bruce Lessey, Chandrakant Tayade","doi":"10.1093/jimmun/vkae021","DOIUrl":"10.1093/jimmun/vkae021","url":null,"abstract":"<p><p>Endometriosis is a chronic disorder in which endometrial-like tissue presents outside the uterus. Patients with endometriosis have been shown to exhibit aberrant immune responses within the lesion microenvironment and in circulation which contribute to the development of endometriosis. Thymic stromal lymphopoietin (TSLP) is an alarmin involved in cell proliferation and the induction of T helper 2 (Th2) inflammation in various diseases, such as asthma, atopic dermatitis, and pancreatic and breast cancer. Recent studies have detected TSLP within endometriotic lesions and shown that its concentrations are elevated in the peritoneal fluid of patients compared with control subjects. However, its role in disease pathophysiology remains unclear. Here, we compared TSLP messenger RNA and protein expression between patient eutopic endometrium, endometriotic lesions, and control endometrial samples. We also assessed its effect on the proliferation and apoptosis of human endometriosis-representative cell lines, as well as on lesion development and inflammation in a mouse model of the disease. We demonstrated that TSLP expression was elevated in the stroma of patient endometriotic lesions compared with control endometrial samples. In cell lines, TSLP treatment reduced the apoptosis of endometrial stromal cells and promoted the proliferation of THP-1 cells. In mice induced with endometriosis, TSLP treatment induced a Th2 immune response within the lesion microenvironment, and led to TSLP receptor modulation in macrophages, dendritic cells, and CD4+ T cells. Furthermore, treatment increased murine endometriotic lesion proliferation. Overall, these results suggest that TSLP modulates the endometriotic lesion microenvironment and promotes a Th2 immune response that could support lesion development.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}