Journal of immunology最新文献

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In vivo antibody labeling route and fluorophore dictate labeling efficiency, sensitivity, and longevity. 体内抗体标记途径和荧光团决定了标记效率、灵敏度和使用寿命。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-09 DOI: 10.1093/jimmun/vkae051
Natalie B Hagan, Charles Inaku, Nikesh Kunder, Tayleur White, Thierry Iraguha, Anna Meyer, Kristen E Pauken, Jason M Schenkel
{"title":"In vivo antibody labeling route and fluorophore dictate labeling efficiency, sensitivity, and longevity.","authors":"Natalie B Hagan, Charles Inaku, Nikesh Kunder, Tayleur White, Thierry Iraguha, Anna Meyer, Kristen E Pauken, Jason M Schenkel","doi":"10.1093/jimmun/vkae051","DOIUrl":"10.1093/jimmun/vkae051","url":null,"abstract":"<p><p>Leukocytes migrate through the blood and extravasate into organs to surveil the host for infection or cancer. Recently, we demonstrated that intravenous (IV) anti-CD45.2 antibody labeling allowed for precise tracking of leukocyte migration. However, the narrow labeling window can make this approach challenging for tracking rare migration events. Here, we show that altering antibody administration route and fluorophore can significantly extend the antibody active labeling time. We found that while both IV and intraperitoneal (IP) anti-CD45.2 antibody labeled circulating leukocytes after injection, they had different kinetic properties that impacted labeling time and intensity. Quantification of circulating antibody revealed that while unbound IV anti-CD45.2 antibody rapidly decreased, unbound IP anti-CD45.2 antibody increased over 1 h. Using in vitro and in vivo serial dilution assays, we found that Alexa Fluor 647 and Brilliant Blue 700 (BB700) dyes had the greatest labeling sensitivity compared with other fluorophores. However, IP antibody injection with anti-CD45.2 BB700, but not Alexa Fluor 647, resulted in continuous blood leukocyte labeling for over 6 h. Finally, we leveraged IP anti-CD45.2 BB700 antibody to track slower migrating leukocytes into tumors. We found that IP anti-CD45.2 antibody injection allowed for the identification of ∼7 times as many tumor-specific CD8+ T cells that had recently migrated from blood into tumors. Our results demonstrate how different injection routes and fluorophores affect anti-CD45.2 antibody leukocyte labeling and highlight the utility of this approach for defining leukocyte migration in the context of homeostasis and cancer.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615683","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
The cellular factors that impair the germinal center in advanced age. 损害老年生发中心的细胞因子。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-09 DOI: 10.1093/jimmun/vkae039
William S Foster, Edith Marcial-Juárez, Michelle A Linterman
{"title":"The cellular factors that impair the germinal center in advanced age.","authors":"William S Foster, Edith Marcial-Juárez, Michelle A Linterman","doi":"10.1093/jimmun/vkae039","DOIUrl":"https://doi.org/10.1093/jimmun/vkae039","url":null,"abstract":"<p><p>Long-lasting immunological memory is a core feature of the adaptive immune system that allows an organism to have a potent recall response to foreign agents that have been previously encountered. Persistent humoral immunity is afforded by long-lived memory B cells and plasma cells, which can mature in germinal centers (GCs) in secondary lymphoid organs. The development of new GC-derived immunity diminishes with age, thereby impairing our immune system's response to both natural infections and vaccinations. This review will describe the current knowledge of how aging affects the cells and microenvironment of the GC. A greater understanding of how the GC changes with age, and how to circumvent these changes, will be critical for tailoring vaccines for older people. This area of research is critical given the twenty-first century will witness a doubling of the aging population and an increased frequency of pandemics.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615736","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
Development and validation of a high throughput multiplex immunofluorescence assay to detect all human immunoglobulin isotypes and subclasses in human fluids. 开发和验证一种高通量多重免疫荧光测定法,用于检测人体液中所有人免疫球蛋白同型和亚类。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-06 DOI: 10.1093/jimmun/vkae048
Arthur H Van Stigt, Maaike Nederend, Gaby Smits, Marjan Kuijer, Rutger M Schepp, Pieter G Van Gageldonk, Anneke H Hellinga, Robert S Van Binnendijk, Louis J Bont, Belinda Van't Land, Gerco Den Hartog, Jeanette H W Leusen
{"title":"Development and validation of a high throughput multiplex immunofluorescence assay to detect all human immunoglobulin isotypes and subclasses in human fluids.","authors":"Arthur H Van Stigt, Maaike Nederend, Gaby Smits, Marjan Kuijer, Rutger M Schepp, Pieter G Van Gageldonk, Anneke H Hellinga, Robert S Van Binnendijk, Louis J Bont, Belinda Van't Land, Gerco Den Hartog, Jeanette H W Leusen","doi":"10.1093/jimmun/vkae048","DOIUrl":"https://doi.org/10.1093/jimmun/vkae048","url":null,"abstract":"<p><p>Antibodies in human milk protect infants against infections, but currently no assay is described that is able to simultaneously measure all 9 antibody isotypes and subclasses immunoglobulins in human fluids, such as human milk. Our cohort \"Protecting against Respiratory tract Infections through human Milk Analysis\" (PRIMA) is focused on the relation between the occurrence of respiratory infections during the first year of life and concentration of maternal antibodies in breastfeeding. We developed and successfully validated a multiplex assay that is able to measure all nine antibody isotypes and subclasses in human plasma and milk (regardeless of the pathogen specificity), using a small sample volume. We used a multiplex immunofluorescence assay (MIA) requiring a minimal sample volume of 25 µl. Commercially available human isotype standards were used in spiking experiments to exclude the presence of cross reactivity. In addition, we prevented signal quenching by milk by determining the optimal dilution of human milk. In conclusion, we have developed a low-volume multiplex assay, that, for the first time, can reliably quantify functionally intact antibodies of all known human isotypes and subclasses and that is able to measure both kappa and lambda heavy chain antibodies. This assay can easily be implemented in other academic labs.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615579","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
Depletion of eosinophils during sensitization but not challenge phase in mice blocks the development of food allergy early in life. 小鼠致敏期而非激食期嗜酸性粒细胞的消耗可阻断生命早期食物过敏的发展。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-06 DOI: 10.1093/jimmun/vkae044
Haoran Gao, Allison E Kosins, Joel A Ochoa, Elizabeth A Jacobsen, Joan M Cook-Mills
{"title":"Depletion of eosinophils during sensitization but not challenge phase in mice blocks the development of food allergy early in life.","authors":"Haoran Gao, Allison E Kosins, Joel A Ochoa, Elizabeth A Jacobsen, Joan M Cook-Mills","doi":"10.1093/jimmun/vkae044","DOIUrl":"https://doi.org/10.1093/jimmun/vkae044","url":null,"abstract":"<p><p>Food allergy can be life threatening and often develops early in life, especially in infants and children with atopic dermatitis. Food allergy is induced in neonatal mice with skin barrier mutations (Flaky Tail, FT+/- mice with filaggrin and mattrin gene mutations) by epicutaneous sensitization with co-exposures to the food allergen peanut extract (PNE), the environmental allergen Alternaria alternata (Alt), and detergent (4% SDS); oral PNE-challenge induces anaphylaxis. Sensitization in these neonates also induces eosinophil infiltration into the skin and elevates skin expression of eotaxins (CCL11 and CCL24). However, roles for eosinophils in food allergy are not known. In this study, the iPhil+/- FT+/- pups, which have an inducible eosinophil-deficiency upon injection of diphtheria toxin (DTX), were sensitized and then received PNE by gavage to assess anaphylaxis. DTX depletion of eosinophils, during sensitization and oral PNE-challenge, blocked the recruitment and activation of mast cells, blocked the Alt+PNE-induced increase in plasma IL-33 and OSM, attenuated serum PNE-specific IgE/IgG1/IgG2b, and blocked oral-PNE-induced anaphylaxis. Anti-IL-5 depletion of eosinophils during sensitization/challenge also blocked anaphylaxis. When eosinophils were depleted during allergen-skin-sensitization and restored before oral PNE-challenge, anaphylaxis was blocked. In contrast, when eosinophils were present during allergen-skin-sensitization but then depleted during oral PNE-challenge, anaphylaxis was not blocked. Together, these data indicate that although eosinophils are not necessary during oral food allergen-induced anaphylaxis, eosinophils have a critical role during the development of food allergy early in life by regulating the sensitization-induced increase in mast cell numbers and food allergen-specific IgE.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615572","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
Aging and neurodegeneration: when systemic dysregulations affect brain macrophage heterogeneity. 衰老和神经退行性变:当系统性失调影响脑巨噬细胞异质性时。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-06 DOI: 10.1093/jimmun/vkae034
Paul Joly, Reyhane Labsy, Aymeric Silvin
{"title":"Aging and neurodegeneration: when systemic dysregulations affect brain macrophage heterogeneity.","authors":"Paul Joly, Reyhane Labsy, Aymeric Silvin","doi":"10.1093/jimmun/vkae034","DOIUrl":"https://doi.org/10.1093/jimmun/vkae034","url":null,"abstract":"<p><p>Microglia, the major population of brain resident macrophages, differentiate from yolk sac progenitors in the embryo and play multiple nonimmune roles in brain organization throughout development and life. Various microglia subtypes have been described by transcriptomic and proteomic signatures, involved metabolic pathways, morphology, intracellular complexity, time of residency, and ontogeny, both in development and in disease settings. Such macrophage heterogeneity increases with aging or neurodegeneration. Monocytes' infiltration and differentiation into monocyte-derived macrophages (MDMs) in the brain contribute to this diversity. Microbiota's role in brain diseases has been recently highlighted, revealing how microbial signals, such as metabolites, influence microglia and MDMs. In this brief review, we describe how these signals can influence microglia through their sensome and shape MDMs from their development in the bone marrow to their differentiation in the brain. Monocytes could then be a crucial player in the constitution of a dysbiotic gut-brain axis in neurodegenerative diseases and aging.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615415","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
Quantitative detection of the HVEM-BTLA checkpoint receptor cis-complex in human lymphocytes. 人淋巴细胞HVEM-BTLA检查点受体顺式复合体的定量检测。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-05 DOI: 10.1093/jimmun/vkae057
Shane Atwell, Timothy C Cheung, Elaine M Conner, Carolyn Ho, Jiawen Huang, Erin L Harryman, Ricky Lieu, Stacie Lim, Wai W Lin, Diana I Ruiz, Andrew C Vendel, Carl F Ware
{"title":"Quantitative detection of the HVEM-BTLA checkpoint receptor cis-complex in human lymphocytes.","authors":"Shane Atwell, Timothy C Cheung, Elaine M Conner, Carolyn Ho, Jiawen Huang, Erin L Harryman, Ricky Lieu, Stacie Lim, Wai W Lin, Diana I Ruiz, Andrew C Vendel, Carl F Ware","doi":"10.1093/jimmun/vkae057","DOIUrl":"10.1093/jimmun/vkae057","url":null,"abstract":"<p><p>The herpesvirus entry mediator (HVEM) (TNFRSF14) engagement of the checkpoint inhibitory receptor B and T lymphocyte attenuator (BTLA) limits immune responses of T and B lymphocytes. HVEM and BTLA form signaling complexes in trans and when coexpressed, complexes in cis, creating a unique immune checkpoint. The function of the HVEM-BTLA cis-complex is not well understood primarily due to a lack of reagents that specifically measure the HVEM-BTLA cis-complex. We describe here a method to generate antibodies to receptor-ligand complexes using fusion immunogens, in this case, a BTLA-HVEM fusion protein. We identified 2 closely related antibodies that specifically recognize the HVEM-BTLA complex on the cell surface. In experiments utilizing the anti-HVEM-BTLA complex-specific antibody together with subunit-specific BTLA monoclonal antibodies, we were able to determine the precise ratio of free to cis-complexed BTLA on subpopulations of human lymphocytes. This is the first direct quantification of the HVEM-BTLA cis-complex. The method described here should apply to the detection of other receptor-ligand complexes.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615656","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
Comparison of human macrophages derived from peripheral blood and bone marrow. 人外周血与骨髓巨噬细胞的比较。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-05 DOI: 10.1093/jimmun/vkae032
Hannah L Smith, Russell B Foxall, Patrick J Duriez, Emma L Teal, Adam D Hoppe, Janos M Kanczler, Juliet C Gray, Stephen A Beers
{"title":"Comparison of human macrophages derived from peripheral blood and bone marrow.","authors":"Hannah L Smith, Russell B Foxall, Patrick J Duriez, Emma L Teal, Adam D Hoppe, Janos M Kanczler, Juliet C Gray, Stephen A Beers","doi":"10.1093/jimmun/vkae032","DOIUrl":"https://doi.org/10.1093/jimmun/vkae032","url":null,"abstract":"<p><p>Macrophage differentiation, phenotype, and function have been assessed extensively in vitro by predominantly deriving human macrophages from peripheral blood. It is accepted that there are differences between macrophages isolated from different human tissues; however, the importance of anatomical source for in vitro differentiation and characterization is less clear. Here, phenotype and function were evaluated between human macrophages derived from bone marrow or peripheral blood. Macrophages were differentiated by adherence of heterogenous cell populations or CD14 isolation and polarized with IFNγ and LPS or IL-4 and IL-13 for 48 hours before evaluation of phenotype and phagocytic capacity. The presence of stromal cells in bone marrow heterogenous cultures resulted in a reduction in macrophage purity compared to peripheral blood, which was negated after CD14 isolation. Phenotypically, monocyte-derived macrophages (MDMs) derived from peripheral blood and bone marrow resulted in similar expression of classical and polarized macrophages markers, including CD14, HLA-DR, CD38, and CD40 (increased after IFNγ/LPS), and CD11b and CD206 (elevated after IL-4/IL-13). Functionally, these cells also showed similar levels of Fc-independent and Fc-dependent phagocytosis, although there was a nonsignificant reduction of Fc-dependent phagocytosis in the bone marrow derived macrophages after IFNγ/LPS stimulation. In summary, we have identified that human MDMs differentiated from peripheral blood and bone marrow showed similar characteristics and functionality, suggesting that isolating cells from different anatomical niches does not affect macrophage differentiation after CD14 isolation. Consequently, due to high yield and ready availability peripheral blood derived macrophages are still the most suitable source.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615558","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
Zebrafish (Danio rerio) TDP43 negatively regulates PKZ-IRF3-mediated IFN I response. 斑马鱼(Danio rerio) TDP43负调控pkz - irf3介导的IFN I反应。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-05 DOI: 10.1093/jimmun/vkae035
Tingting Yu, Miaomiao Li, Meifeng Li, Shanghong Wang, Zhiqing Feng, Hongying Zhang, Jiwei Liu, Huiling Mao, Dongming Li, Chengyu Hu, Xiaowen Xu
{"title":"Zebrafish (Danio rerio) TDP43 negatively regulates PKZ-IRF3-mediated IFN I response.","authors":"Tingting Yu, Miaomiao Li, Meifeng Li, Shanghong Wang, Zhiqing Feng, Hongying Zhang, Jiwei Liu, Huiling Mao, Dongming Li, Chengyu Hu, Xiaowen Xu","doi":"10.1093/jimmun/vkae035","DOIUrl":"https://doi.org/10.1093/jimmun/vkae035","url":null,"abstract":"<p><p>Transactive response DNA binding protein 43 kD (TDP43), encoded by the tardbp gene, is a member of heterogenous nuclear ribonucleoproteins family. In this study, a gradual upregulation of TDP43 messenger RNA was observed in either Ctenopharyngodon idella kidney cells or zebrafish following stimulation with B-DNA, grass carp reovirus, or spring viremia of carp virus. Moreover, grass carp reovirus stimulation enhances the dimerization, phosphorylation, and cytoplasm-to-nucleus translocation of TDP43 in zebrafish (DrTDP43). Type I interferon (IFN I) expression is inhibited in a dose-dependent manner in the cells transfected with DrTDP43 under GCRV stimulation. These results indicated that DrTDP43 is involved in innate immune response and serves as a negative regulator of IFN I expression. To determine DrTDP43-dependent downstream pathway in innate immunity, the substrate of DrTDP43 was studied. It is known that IFN I expression can be activated by PKZ via IRF3 dependent pathway. Our results found that DrTDP43 can be interacted with PKZ, suggesting that the downregulation of IFN I by DrTDP43 may attribute to the inhibition of PKZ activity. Multiple DrTDP43 mutants were constructed to further reveal the mechanism of TDP43-PKZ-mediated IFN I response. Apart from the N-terminal domain, RNA recognition motif 1, RNA recognition motif 2, and low-complexity domain domains of DrTDP43 were all found to be involved in inhibiting phosphorylation of PKZ. In vivo, knockdown of TDP43 in zebrafish embryos improved embryo survival rate upon viral infection and upregulated expression of IFN I. In summary, our findings demonstrate that DrTDP43 is a negative regulator of IFN I expression through the inhibition of the PKZ-IRF3-dependent pathway.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615744","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
Gut IgA-antibody secreting cells segregate into four Blimp1+ subsets based on differential expression of IgA and Ki-67 and are retained following prolonged αCD20 B cell depletion in mice. 小鼠肠道IgA抗体分泌细胞根据IgA和Ki-67的差异表达分化为4个Blimp1+亚群,并在αCD20 B细胞长时间耗尽后保留。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-05 DOI: 10.1093/jimmun/vkae046
Savannah D Neu, Cody J Gurski, Nathan J Meinhardt, Kevin C Jennings, Bonnie N Dittel
{"title":"Gut IgA-antibody secreting cells segregate into four Blimp1+ subsets based on differential expression of IgA and Ki-67 and are retained following prolonged αCD20 B cell depletion in mice.","authors":"Savannah D Neu, Cody J Gurski, Nathan J Meinhardt, Kevin C Jennings, Bonnie N Dittel","doi":"10.1093/jimmun/vkae046","DOIUrl":"https://doi.org/10.1093/jimmun/vkae046","url":null,"abstract":"<p><p>B cell depletion is an efficacious therapy for multiple sclerosis, but its long-term safety profile in the gastrointestinal tract has not been specifically studied. This is of importance because the gut is the largest reservoir of IgA in the body, which maintains gut homeostasis in part by regulating the composition of the gut microbiota. This was addressed by development of a prolonged B cell depletion model using human CD20 transgenic mice and B cell depletion with the anti-human CD20 antibodies rituximab, a humanized mouse monoclonal, and 2H7, the mouse precursor to ocrelizumab. Both antibodies depleted B cells in the spleen, mesenteric lymph nodes, small intestine, and large intestine, with 2H7 being more efficient. Because gut IgA+ antibody secreting cells (ASC) are poorly defined a flow cytometry strategy was developed using differential expression of IgA and Ki-67 by Blimp1+ cells that identified four IgA-ASC subsets across a developmental spectrum. Neither antibody was efficacious in depleting of any IgA-ASC subset in the intestines. Consequently, fecal IgA levels and percentage of IgA-bound fecal microbes were unaltered. Cumulatively, these studies demonstrate that prolonged B cell-depletion did not substantially impact IgA levels nor overall gut health, providing important insight into the safety profile of B cell depletion drugs.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615676","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
Myeloid-derived IL-33 drives γδ T cell-dependent resistance against cutaneous infection by Strongyloides ratti. 髓源性IL-33驱动γδ T细胞依赖性抗鼠圆形线虫皮肤感染
IF 3.6 3区 医学
Journal of immunology Pub Date : 2025-03-04 DOI: 10.1093/jimmun/vkae038
Erin Evonne Jean, Heather Lynn Rossi, Li Yin Hung, Juan M Inclan-Rico, De'Broski R Herbert
{"title":"Myeloid-derived IL-33 drives γδ T cell-dependent resistance against cutaneous infection by Strongyloides ratti.","authors":"Erin Evonne Jean, Heather Lynn Rossi, Li Yin Hung, Juan M Inclan-Rico, De'Broski R Herbert","doi":"10.1093/jimmun/vkae038","DOIUrl":"10.1093/jimmun/vkae038","url":null,"abstract":"<p><p>Interleukin 33 (IL-33) is a pleiotropic cytokine released from diverse cell types that regulate both pro- and anti-inflammatory responses during pathogen infection. However, it remains unclear whether IL-33 controls key aspects of cutaneous immunity against skin-penetrating parasites. In this study, mice percutaneously infected with the parasitic helminth Strongyloides ratti were investigated to understand mechanisms of anamnestic immunity at the skin barrier. Surprisingly, mice lacking the Type 2 transcription factor STAT6 (signal transducer and activator of transcription 6) had no defects in secondary resistance to infection, whereas IL-33 gene deficiency or local blockade of IL-33 receptor (ST2) signaling abrogated host resistance. Depletion of CD4+ T cells or type 2 innate lymphoid cells had only a moderate impact on protection, but the loss of γδ T cells completely ablated cutaneous immunity against rechallenge. We identified a CD62Lhi IL-33 receptor (ST2)-expressing γδ T cell population that accumulated in the skin of protected mice that was dependent upon IL-33 expression in myeloid lineage antigen-presenting cells. This work suggests a previously unrecognized mechanism wherein noncanonical type 2 immunity operates through myeloid antigen-presenting cells and skin γδ T cells to adaptively repel skin-penetrating helminth larvae.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615698","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
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