Journal of immunology最新文献_第9页

Obesity Inhibits Alveolar Macrophage Responses to Pseudomonas aeruginosa Pneumonia via Upregulation of Prostaglandin E2 in Male, but Not Female, Mice. 肥胖通过上调雄性小鼠而非雌性小鼠的前列腺素 E2抑制肺泡巨噬细胞对铜绿假单胞菌肺炎的反应

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2400140

Gabrielle P Entrup, Aayush Unadkat, Helen I Warheit-Niemi, Brooke Thomas, Stephen J Gurczynski, Yuxiao Cui, Andrew M Smith, Katherine A Gallagher, Bethany B Moore, Kanakadurga Singer

{"title":"Obesity Inhibits Alveolar Macrophage Responses to Pseudomonas aeruginosa Pneumonia via Upregulation of Prostaglandin E2 in Male, but Not Female, Mice.","authors":"Gabrielle P Entrup, Aayush Unadkat, Helen I Warheit-Niemi, Brooke Thomas, Stephen J Gurczynski, Yuxiao Cui, Andrew M Smith, Katherine A Gallagher, Bethany B Moore, Kanakadurga Singer","doi":"10.4049/jimmunol.2400140","DOIUrl":"10.4049/jimmunol.2400140","url":null,"abstract":"Obesity is associated with increased morbidity and mortality during bacterial pneumonia. Cyclooxygenase-2 (COX-2) and PGE2 have been shown to be upregulated in patients who are obese. In this study, we investigated the role of obesity and PGE2 in bacterial pneumonia and how inhibition of PGE2 improves antibacterial functions of macrophages. C57BL/6J male and female mice were fed either a normal diet (ND) or high-fat diet (HFD) for 16 wk. After this time, animals were infected with Pseudomonas aeruginosa in the lung. In uninfected animals, alveolar macrophages were extracted for either RNA analysis or to be cultured ex vivo for functional analysis. HFD resulted in changes in immune cell numbers in both noninfected and infected animals. HFD animals had increased bacterial burden compared with ND animals; however, male HFD animals had higher bacterial burden compared with HFD females. Alveolar macrophages from HFD males had decreased ability to phagocytize and kill bacteria and were shown to have increased cyclooxygenase-2 and PGE2. Treating male, but not female, alveolar macrophages with PGE2 leads to increases in cAMP and decreased bacterial phagocytosis. Treatment with lumiracoxib-conjugated nanocarriers targeting alveolar macrophages improves bacterial phagocytosis and clearance in both ND and HFD male animals. Our study highlights that obesity leads to worse morbidity during bacterial pneumonia in male mice because of elevated PGE2. In addition, we uncover a sex difference in both obesity and infection, because females produce high basal PGE2 but because of a failure to signal via cAMP do not display impaired phagocytosis.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437011","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}

引用次数: 0

Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development. 内质网应激反应介质 IRE-1α 促进宿主树突状细胞在移植物抗宿主疾病发展中的作用

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2300616

Hee-Jin Choi, Yongxia Wu, Brianyell McDaniel Mims, Allison Pugel, Chih-Hang Anthony Tang, Linlu Tian, Chih-Chi Andrew Hu, Xue-Zhong Yu

{"title":"Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development.","authors":"Hee-Jin Choi, Yongxia Wu, Brianyell McDaniel Mims, Allison Pugel, Chih-Hang Anthony Tang, Linlu Tian, Chih-Chi Andrew Hu, Xue-Zhong Yu","doi":"10.4049/jimmunol.2300616","DOIUrl":"10.4049/jimmunol.2300616","url":null,"abstract":"Allogeneic hematopoietic cell transplantation is an effective treatment for hematologic malignancies, but the complications such as graft-versus-host disease (GVHD) can limit its benefit. The conditioning regimens before transplant, including chemotherapy or irradiation, can trigger endoplasmic reticulum stress. IRE-1α is a major endoplasmic reticulum stress mediator that can further activate both spliced XBP-1 (XBP-1s) and regulated IRE-1-dependent decay (RIDD). IRE-1α-XBP-1s signaling controls dendritic cell (DC) differentiation and Ag presentation, crucial in GVHD progression. In this study, we used DC-specific XBP-1-deficient mice as donors or recipients and observed that XBP-1s was crucial for host DCs in the induction of GVHD but dispensable for the graft-versus-leukemia response. To specifically target IRE-1α in the host, we treated recipient mice with the IRE-1α inhibitor B-I09 for 3 d prior to bone marrow transplantation, which significantly suppressed GVHD development while maintaining the graft-versus-leukemia effect. XBP-1-deficient or BI09-treated recipients showed reduced DC survival after irradiation and bone marrow transplantation. Inhibition of IRE-1α also led to a reduction in DC alloreactivity, subsequently decreasing the proliferation and activation of allogeneic T cells. With further study using RIDD-deficient DCs, we observed that RIDD was also required for optimal DC activation. Taken together, XBP-1s and RIDD both promote host DC survival and alloreactivity that contribute to GVHD development.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306133","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}

引用次数: 0

B Cells of Early-life Origin Defined by RAG2-based Lymphoid Cell Tracking under Native Hematopoietic Conditions. 在原生造血条件下通过基于 RAG2 的淋巴细胞追踪确定生命早期起源的 B 细胞

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2400072

Keiko Fujisaki, Shogo Okazaki, Shuhei Ogawa, Miyama Takeda, Eiji Sugihara, Kenichi Imai, Seiya Mizuno, Satoru Takahashi, Ryo Goitsuka

{"title":"B Cells of Early-life Origin Defined by RAG2-based Lymphoid Cell Tracking under Native Hematopoietic Conditions.","authors":"Keiko Fujisaki, Shogo Okazaki, Shuhei Ogawa, Miyama Takeda, Eiji Sugihara, Kenichi Imai, Seiya Mizuno, Satoru Takahashi, Ryo Goitsuka","doi":"10.4049/jimmunol.2400072","DOIUrl":"10.4049/jimmunol.2400072","url":null,"abstract":"During the perinatal period, the immune system sets the threshold to select either response or tolerance to environmental Ags, which leads to the potential to provide a lifetime of protection and health. B-1a B cells have been demonstrated to develop during this perinatal time window, showing a unique and restricted BCR repertoire, and these cells play a major role in natural Ab secretion and immune regulation. In the current study, we developed a highly efficient temporally controllable RAG2-based lymphoid lineage cell labeling and tracking system and applied this system to understand the biological properties and contribution of B-1a cells generated at distinct developmental periods to the adult B-1a compartments. This approach revealed that B-1a cells with a history of RAG2 expression during the embryonic and neonatal periods dominate the adult B-1a compartment, including those in the bone marrow (BM), peritoneal cavity, and spleen. Moreover, the BCR repertoire of B-1a cells with a history of RAG2 expression during the embryonic period was restricted, becoming gradually more diverse during the neonatal period, and then heterogeneous at the adult stage. Furthermore, more than half of plasmablasts/plasma cells in the adult BM had embryonic and neonatal RAG2 expression histories. Moreover, BCR analysis revealed a high relatedness between BM plasmablasts/plasma cells and B-1a cells derived from embryonic and neonatal periods, suggesting that these cell types have a common origin. Taken together, these findings define, under native hematopoietic conditions, the importance in adulthood of B-1a cells generated during the perinatal period.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317537","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}

引用次数: 0

Distinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells. 生命早期扁桃体调节性 T 细胞的不同定位、转录谱和功能。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2300890

Shivali Verma, Marissa C Bradley, Joshua Gray, Pranay Dogra, Daniel P Caron, Sarah Maurrasse, Eli Grunstein, Erik Waldman, Minyoung Jang, Kalpana Pethe, Donna L Farber, Thomas J Connors

{"title":"Distinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells.","authors":"Shivali Verma, Marissa C Bradley, Joshua Gray, Pranay Dogra, Daniel P Caron, Sarah Maurrasse, Eli Grunstein, Erik Waldman, Minyoung Jang, Kalpana Pethe, Donna L Farber, Thomas J Connors","doi":"10.4049/jimmunol.2300890","DOIUrl":"10.4049/jimmunol.2300890","url":null,"abstract":"CD4+ regulatory T cells (Tregs) are key orchestrators of the immune system, fostering the establishment of protective immunity while preventing deleterious responses. Infancy and childhood are crucial periods of rapid immunologic development, but how Tregs mediate immune responses at these earliest timepoints of human life is poorly understood. In this study, we compare blood and tissue (tonsil) Tregs across pediatric and adult subjects to investigate age-related differences in Treg biology. We observed increased FOXP3 expression and proportions of Tregs in tonsil compared with paired blood samples in children. Within tonsil, early life Tregs accumulated in extrafollicular regions with cellular interactions biased toward CD8+ T cells. Tonsil Tregs in both children and adults expressed transcriptional profiles enriched for lineage defining signatures and canonical functionality compared with blood, suggesting tissue as the primary site of Treg activity. Early life tonsil Tregs transcriptional profiles were further defined by pathways associated with activation, proliferation, and polyfunctionality. Observed differences in pediatric tonsil Treg transcriptional signatures were associated with phenotypic differences, high proliferative capacity, and robust production of IL-10 compared with adult Tregs. These results identify tissue as a major driver of Treg identity, provide new insights into developmental differences in Treg biology across the human lifespan, and demonstrate unique functional properties of early life Tregs.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437010","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}

引用次数: 0

CCL22 Induces the Polarization of Immature Dendritic Cells into Tolerogenic Dendritic Cells in Radiation-Induced Lung Injury through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 Signaling Pathway. CCL22通过CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1信号通路诱导辐射诱导的肺损伤中未成熟树突状细胞极化为耐受性树突状细胞

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2300718

Benbo Liu, Yilong Wang, Liping Ma, Guo Chen, Zhihua Yang, Maoxiang Zhu

{"title":"CCL22 Induces the Polarization of Immature Dendritic Cells into Tolerogenic Dendritic Cells in Radiation-Induced Lung Injury through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 Signaling Pathway.","authors":"Benbo Liu, Yilong Wang, Liping Ma, Guo Chen, Zhihua Yang, Maoxiang Zhu","doi":"10.4049/jimmunol.2300718","DOIUrl":"10.4049/jimmunol.2300718","url":null,"abstract":"Recruitment of immune cells to the injury site plays a pivotal role in the pathology of radiation-associated diseases. In this study, we investigated the impact of the chemokine CCL22 released from alveolar type II epithelial (AT2) cells after irradiation on the recruitment and functional changes of dendritic cells (DCs) in the development of radiation-induced lung injury (RILI). By examining changes in CCL22 protein levels in lung tissue of C57BL/6N mice with RILI, we discovered that ionizing radiation increased CCL22 expression in irradiated alveolar AT2 cells, as did MLE-12 cells after irradiation. A transwell migration assay revealed that CCL22 promoted the migration of CCR4-positive DCs to the injury site, which explained the migration of pulmonary CCR4-positive DCs in RILI mice in vivo. Coculture experiments demonstrated that, consistent with the response of regulatory T cells in the lung tissue of RILI mice, exogenous CCL22-induced DCs promoted regulatory T cell proliferation. Mechanistically, we demonstrated that Dectin2 and Nr4a2 are key targets in the CCL22 signaling pathway, which was confirmed in pulmonary DCs of RILI mice. As a result, CCL22 upregulated the expression of PD-L1, IL-6, and IL-10 in DCs. Consequently, we identified a mechanism in which CCL22 induced DC tolerance through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 pathway. Collectively, these findings demonstrated that ionizing radiation stimulates the expression of CCL22 in AT2 cells to recruit DCs to the injury site and further polarizes them into a tolerant subgroup of CCL22 DCs to regulate lung immunity, ultimately providing potential therapeutic targets for DC-mediated RILI.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296211","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}

引用次数: 0

Inflammasomes at the Foundation of Inflammatory Cell Death Complexes. 炎症细胞死亡复合物的基础炎症小体

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2400288

Rebecca E Tweedell, Thirumala-Devi Kanneganti

引用次数: 0

Reappraising the Role of T Cell-Derived IFN-γ in Restriction of Mycobacterium tuberculosis in the Murine Lung. 重新评估 T 细胞产生的 IFN-γ 在限制小鼠肺部结核分枝杆菌中的作用

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-08-01 DOI: 10.4049/jimmunol.2400145

Karolina Maciag, Courtney R Plumlee, Sara B Cohen, Benjamin H Gern, Kevin B Urdahl

引用次数: 0

CCR1 and CCR2 Coexpression on Monocytes Is Nonredundant and Delineates a Distinct Monocyte Subpopulation. 单核细胞上的 CCR1 和 CCR2 共表达是非冗余的，并划分出一个不同的单核细胞亚群。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-07-15 DOI: 10.4049/jimmunol.2400007

Laura Medina-Ruiz, Robin Bartolini, Heather Mathie, Heba A Halawa, Madeleine Cunningham, Gerard J Graham

{"title":"CCR1 and CCR2 Coexpression on Monocytes Is Nonredundant and Delineates a Distinct Monocyte Subpopulation.","authors":"Laura Medina-Ruiz, Robin Bartolini, Heather Mathie, Heba A Halawa, Madeleine Cunningham, Gerard J Graham","doi":"10.4049/jimmunol.2400007","DOIUrl":"10.4049/jimmunol.2400007","url":null,"abstract":"The interactions between chemokines and their receptors, particularly in the context of inflammation, are complex, with individual receptors binding multiple ligands and individual ligands interacting with multiple receptors. In addition, there are numerous reports of simultaneous coexpression of multiple inflammatory chemokine receptors on individual inflammatory leukocyte subtypes. Overall, this has previously been interpreted as redundancy and proposed as a protective mechanism to ensure that the inflammatory response is robust. By contrast, we have hypothesized that the system is not redundant but exquisitely subtle. Our interests relate to the receptors CCR1, CCR2, CCR3, and CCR5, which, together, regulate nonneutrophilic myeloid cell recruitment to inflammatory sites. In this study, we demonstrate that although most murine monocytes exclusively express CCR2, there is a small subpopulation that is expanded during inflammation and coexpresses CCR1 and CCR2. Combinations of transcript and functional analysis demonstrate that this is not redundant expression and that coexpression of CCR1 and CCR2 marks a phenotypically distinct population of monocytes characterized by expression of genes otherwise typically associated with neutrophils. Single-cell RNA sequencing confirms this as a monodisperse population of atypical monocytes. This monocytic population has previously been described as having immunosuppressive activity. Overall, our data confirm combinatorial chemokine receptor expression by a subpopulation of monocytes but demonstrate that this is not redundant expression and marks a discrete monocytic population.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200102","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}

引用次数: 0

Human Alveolar and Monocyte-Derived Human Macrophage Responses to Mycobacterium tuberculosis. 人类肺泡和单核细胞衍生的人类巨噬细胞对结核分枝杆菌的反应

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-07-15 DOI: 10.4049/jimmunol.2300885

Monica Campo, Kimberly A Dill-McFarland, Glenna J Peterson, Basilin Benson, Shawn J Skerrett, Thomas R Hawn

{"title":"Human Alveolar and Monocyte-Derived Human Macrophage Responses to Mycobacterium tuberculosis.","authors":"Monica Campo, Kimberly A Dill-McFarland, Glenna J Peterson, Basilin Benson, Shawn J Skerrett, Thomas R Hawn","doi":"10.4049/jimmunol.2300885","DOIUrl":"10.4049/jimmunol.2300885","url":null,"abstract":"Alveolar macrophages (AMs) and recruited monocyte-derived macrophages (MDMs) mediate early lung immune responses to Mycobacterium tuberculosis. Differences in the response of these distinct cell types are poorly understood and may provide insight into mechanisms of tuberculosis pathogenesis. The objective of this study was to determine whether M. tuberculosis induces unique and essential antimicrobial pathways in human AMs compared with MDMs. Using paired human AMs and 5-d MCSF-derived MDMs from six healthy volunteers, we infected cells with M. tuberculosis H37Rv for 6 h, isolated RNA, and analyzed transcriptomic profiles with RNA sequencing. We found 681 genes that were M. tuberculosis dependent in AMs compared with MDMs and 4538 that were M. tuberculosis dependent in MDMs, but not AMs (false discovery rate [FDR] < 0.05). Using hypergeometric enrichment of DEGs in Broad Hallmark gene sets, we found that type I and II IFN Response were the only gene sets selectively induced in M. tuberculosis-infected AM (FDR < 0.05). In contrast, MYC targets, unfolded protein response and MTORC1 signaling, were selectively enriched in MDMs (FDR < 0.05). IFNA1, IFNA8, IFNE, and IFNL1 were specifically and highly upregulated in AMs compared with MDMs at baseline and/or after M. tuberculosis infection. IFNA8 modulated M. tuberculosis-induced proinflammatory cytokines and, compared with other IFNs, stimulated unique transcriptomes. Several DNA sensors and IFN regulatory factors had higher expression at baseline and/or after M. tuberculosis infection in AMs compared with MDMs. These findings demonstrate that M. tuberculosis infection induced unique transcriptional responses in human AMs compared with MDMs, including upregulation of the IFN response pathway and specific DNA sensors.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246756","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}

引用次数: 0

Cutting Edge: ATP13A2 Is an Endolysosomal Regulator of TLR9/7 Activation in Human Plasmacytoid Dendritic Cells. 前沿：ATP13A2 是人类浆细胞树突状细胞中 TLR9/7 激活的溶酶体内调节器。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-07-15 DOI: 10.4049/jimmunol.2300733

Purbita Bandopadhyay, Jafar Sarif, Ranit D'Rozario, Chinky Shiu Chen Liu, Bishnu P Sinha, Md Asmaul Hoque, Koustav Chatterjee, Supriyo Choudhury, Hrishikesh Kumar, Deblina Raychaudhuri, Dipyaman Ganguly

{"title":"Cutting Edge: ATP13A2 Is an Endolysosomal Regulator of TLR9/7 Activation in Human Plasmacytoid Dendritic Cells.","authors":"Purbita Bandopadhyay, Jafar Sarif, Ranit D'Rozario, Chinky Shiu Chen Liu, Bishnu P Sinha, Md Asmaul Hoque, Koustav Chatterjee, Supriyo Choudhury, Hrishikesh Kumar, Deblina Raychaudhuri, Dipyaman Ganguly","doi":"10.4049/jimmunol.2300733","DOIUrl":"10.4049/jimmunol.2300733","url":null,"abstract":"ATPase cation transporting 13A2 (ATP13A2) is an endolysosomal P-type ATPase known to be a polyamine transporter, explored mostly in neurons. As endolysosomal functions are also crucial in innate immune cells, we aimed to explore the potential role of ATP13A2 in the human immunocellular compartment. We found that human plasmacytoid dendritic cells (pDCs), the professional type I IFN-producing immune cells, especially have a prominent enrichment of ATP13A2 expression in endolysosomal compartments. ATP13A2 knockdown in human pDCs interferes with cytokine induction in response to TLR9/7 activation in response to bona fide ligands. ATP13A2 plays this crucial role in TLR9/7 activation in human pDCs by regulating endolysosomal pH and mitochondrial reactive oxygen generation. This (to our knowledge) hitherto unknown regulatory mechanism in pDCs involving ATP13A2 opens up a new avenue of research, given the crucial role of pDC-derived type I IFNs in protective immunity against infections as well as in the immunopathogenesis of myriad contexts of autoreactive inflammation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476743","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}

引用次数: 0