Journal of immunology最新文献

NKG2D ligand expression on NK cells induces NKG2D-mediated cross-tolerization of cytokine signaling and reduces NK cell tumor immunity.

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-08 DOI: 10.1093/jimmun/vkaf030

Zoe K Bedrosian, Elizabeth M Ruark, Neekun Sharma, Rachel B Silverstein, Allison Manning, Lauren Kohlsaat, Mary A Markiewicz

{"title":"NKG2D ligand expression on NK cells induces NKG2D-mediated cross-tolerization of cytokine signaling and reduces NK cell tumor immunity.","authors":"Zoe K Bedrosian, Elizabeth M Ruark, Neekun Sharma, Rachel B Silverstein, Allison Manning, Lauren Kohlsaat, Mary A Markiewicz","doi":"10.1093/jimmun/vkaf030","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf030","url":null,"abstract":"Studies support a role for natural killer (NK) cells in cancer control, making these cells attractive for immunotherapy. One method being tested to make effective NK cells is the ex vivo activation with interleukin (IL)-12, IL-15, and IL-18. We demonstrate that this induces NKG2D ligands on NK cells. By engaging NKG2D, this NKG2D ligand expression eliminated the ability of both mouse and human NK cells to control tumor growth in vivo and in vitro, respectively. NKG2D-NKG2D ligand interaction between mouse NK cells reduced NK cell proliferation, CD25 and T-bet expression, and tumor necrosis factor and interferon γ release. NKG2D signaling induced between human NK cells similarly decreased interferon γ but did not affect T-bet or CD25 expression. These data demonstrate that NKG2D signaling can cross-tolerize cytokine signaling and suggest that eliminating this signaling could be beneficial in NK cell adoptive therapy. Further, these results highlight a need to better delineate effects downstream of NKG2D signaling in human, rather than mouse, NK cells.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811554","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

Lung-resident memory CD4+ T cells are dependent on Batf3. 肺驻留记忆 CD4+ T 细胞依赖于 Batf3。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-04 DOI: 10.1093/jimmun/vkaf035

Antonio M Patterson, Hideki Nakano, Gregory S Whitehead, Christina L Wilkinson, Keiko Nakano, Abdull J Massri, Donald N Cook

引用次数: 0

Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity. 结核病患者的中性粒细胞会根据病情严重程度向促炎和抗炎表型分化。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-04 DOI: 10.1093/jimmun/vkaf010

María Paula Morelli, Candela Martin, Joaquín Miguel Pellegrini, Federico Blanco, Fabiana Bigi, Lorena Ciallella, Rosa Musella, Adriana Rodriguez Mieres, Graciela C de Casado, Domingo Juan Palmero, Verónica Edith García

{"title":"Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity.","authors":"María Paula Morelli, Candela Martin, Joaquín Miguel Pellegrini, Federico Blanco, Fabiana Bigi, Lorena Ciallella, Rosa Musella, Adriana Rodriguez Mieres, Graciela C de Casado, Domingo Juan Palmero, Verónica Edith García","doi":"10.1093/jimmun/vkaf010","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf010","url":null,"abstract":"Neutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient's neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient's neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB's neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780282","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

Sterile production of interferons in the thymus.

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-04 DOI: 10.1093/jimmun/vkaf048

Ryan J Martinez, Kristin A Hogquist

引用次数: 0

The metabolic drivers of IFN-γ release: glycolysis and acetyl CoA ride in the front seat.

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-03 DOI: 10.1093/jimmun/vkaf045

John Henderson, Steven O'Reilly

引用次数: 0

Cutting Edge: Cooperative interferon regulatory factor network shapes the NK-cell antiviral response. 前沿：合作性干扰素调节因子网络塑造了 NK 细胞的抗病毒反应。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-03 DOI: 10.1093/jimmun/vkaf041

Endi K Santosa, Jennifer M Zhang, John C Sauter, Mark Owyong, Joseph C Sun

引用次数: 0

Characterization of autoantibody profiles in clusters of systemic lupus erythematosus using a novel autoantigen discovery technology. 利用新型自身抗原发现技术确定系统性红斑狼疮集群中自身抗体的特征。

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-03 DOI: 10.1093/jimmun/vkae025

Europe B DiCillo, David S Pisetsky, Elisabet Svenungsson, Lina-Marcela Diaz-Gallo, Iva Gunnarsson, Thomas F Tedder

{"title":"Characterization of autoantibody profiles in clusters of systemic lupus erythematosus using a novel autoantigen discovery technology.","authors":"Europe B DiCillo, David S Pisetsky, Elisabet Svenungsson, Lina-Marcela Diaz-Gallo, Iva Gunnarsson, Thomas F Tedder","doi":"10.1093/jimmun/vkae025","DOIUrl":"https://doi.org/10.1093/jimmun/vkae025","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by a wide range of clinical and immunologic manifestations, most prominently, the production of autoantibodies to nuclear components (ANAs). A previous study delineated four SLE patient clusters based on autoantibody expression to common antigens. To further assess autoantibody diversity within these clusters, we surveyed serum autoantibody expression using a novel autoantigen discovery technology, the Antigenome Platform. This phage-based system assesses serum antibody interactions with large protein fragments (up to 250 amino acids) spanning approximately 90% of the human genome. Bound autoantibody targets were identified through next-generation sequencing and robust bioinformatics and statistical analysis. Our study revealed 88, 49, 10, and 24 autoantibodies that expand the characterization of four SLE clusters, including 24 autoantibodies that characterize a cluster of patients lacking common autoantibodies by conventional assays. Further, some autoantibodies identified have potential links to patient disease features. Although SLE is characterized by antinuclear antibody expression, a significant proportion of autoantigens (ranging from 28% to 54%) in each cluster localized to the cytoplasm, which suggests extensive autoreactivity beyond targets in the cell nucleus that formed the original basis of clustering. This study identifies new markers to aid in the clustering and understanding of SLE disease subtypes and provides a rationale for elucidating autoantibody expression in SLE beyond antinuclear antibodies.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780271","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 immunopathogenesis of SARS-CoV-2 infection: Overview of lessons learned in the first 5 years.

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-03 DOI: 10.1093/jimmun/vkaf033

Otto O Yang

{"title":"The immunopathogenesis of SARS-CoV-2 infection: Overview of lessons learned in the first 5 years.","authors":"Otto O Yang","doi":"10.1093/jimmun/vkaf033","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf033","url":null,"abstract":"This review provides a broad overview of lessons learned in the five years since COVID-19 was identified. It is a bimodal disease, starting with an initially virus-driven phase, followed by resolution or ensuing inappropriate immune activation causing severe inflammation that is no longer strictly virus dependent. Humoral immunity is beneficial for preventing or attenuating the early stage, without benefit once the later stage begins. Neutralizing antibodies elicited by natural infection or vaccination are short-lived and highly vulnerable to viral sequence variation. By contrast, cellular immunity, particularly the CD8+ T cell arm, has a role in preventing or attenuating severe disease, is far less susceptible to viral variation, and is longer-lived than antibodies. Finally, an ill-defined phenomenon of prolonged symptoms after acute infection, termed \"long COVID,\" is poorly understood but may involve various immunologic defects that are hyperactivating or immunosuppressive. Remaining issues include needing to better understand the immune dysregulation of severe disease to allow more tailored therapeutic interventions, developing antibody strategies that cope with the viral spike sequence variability, prolonging vaccine efficacy, and unraveling the mechanisms of long COVID to design therapeutic approaches.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780327","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

BCG induced innate immune response heterogeneity and susceptibility to pediatric tuberculosis.

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-02 DOI: 10.1093/jimmun/vkae062

Christine Anterasian, Anele Gela, Temwa-Dango Mwambene, Javeed A Shah, Josh Ivie, Kimberly A Dill-McFarland, Willem A Hanekom, Michael C Kiritsy, Christopher M Sassetti, Munyaradzi Musvosvi, Mark Hatherill, Thomas J Scriba, Thomas R Hawn

{"title":"BCG induced innate immune response heterogeneity and susceptibility to pediatric tuberculosis.","authors":"Christine Anterasian, Anele Gela, Temwa-Dango Mwambene, Javeed A Shah, Josh Ivie, Kimberly A Dill-McFarland, Willem A Hanekom, Michael C Kiritsy, Christopher M Sassetti, Munyaradzi Musvosvi, Mark Hatherill, Thomas J Scriba, Thomas R Hawn","doi":"10.1093/jimmun/vkae062","DOIUrl":"https://doi.org/10.1093/jimmun/vkae062","url":null,"abstract":"Although immune responses to bacillus Calmette-Guerin (BCG)-vaccination and susceptibility to pediatric tuberculosis (TB) vary across individuals, the underlying cellular mechanism regulating this heterogeneity is poorly understood. We used a nested case-control study with a 2-yr prospective observation period to examine whether genetic variation is associated with BCG-induced innate immune responses and susceptibility to pediatric TB (N = 134 cases, 516 controls) in BCG-vaccinated infants. Whole blood collected at 10 wk of age from 189 control infants was stimulated with BCG or media and examined with flow cytometry to measure BCG-induced PDL1, CD40, and cytokine expression in myeloid (mDC) and plasmacytoid (pDC) dendritic cells, monocytes, and neutrophils. We used a cellular and clinical GWAS to assess for associations between genetic variants, BCG-induced innate immune responses, and susceptibility to TB. We identified 11 lead genetic variants at genome-wide level significance associated with BCG-induced cytokine and surface expression markers including PDL1 (5 pDCs, 3 mDCs, 1 monocytes), CD40 (1 mDCs), and IL-6 (1 monocytes). An IGLL1 variant (rs2096522) was associated with mDC CD40 expression (P = 1.6e-08) and was also discovered as a significant variant using a gene-based method. In the clinical GWAS, we identified 39 lead variants mapping to 74 genes suggestive of an association with susceptibility to pediatric TB (P < 1e-05), but no variant reached genome-wide significance. One clinical lead variant in the PDE8A region (rs1023844, P = 9.6e-07) was also an eQTL and associated with BCG-induced monocyte PDL1 expression. In summary, we identified genetic variants associated with heterogeneity in infant BCG-induced innate immune responses with potential immunoregulatory mechanisms.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772402","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

Lung NK cells are sufficient to control viral dissemination during respiratory MCMV infection.

IF 3.6 3区医学

Journal of immunology Pub Date : 2025-04-02 DOI: 10.1093/jimmun/vkaf039

Miles A Mundy, Delia Demers, Laurent Brossay

{"title":"Lung NK cells are sufficient to control viral dissemination during respiratory MCMV infection.","authors":"Miles A Mundy, Delia Demers, Laurent Brossay","doi":"10.1093/jimmun/vkaf039","DOIUrl":"10.1093/jimmun/vkaf039","url":null,"abstract":"Murine cytomegalovirus (MCMV) respiratory dissemination schemes, which mimic natural infection routes, have only recently become an area of investigation. Using an intratracheal (i.t.) infection method, we discovered that the respiratory infection route yields differential infection kinetics compared to the widely used intraperitoneal (i.p.) infection method. Remarkably, we find that respiratory infection results in limited dissemination, with the virus being mostly contained in the pulmonary tissue. Importantly, using Rag1, Ly49H, and natural killer (NK) cell-deficient animals, we find that lung conventional NK (cNK) cells play a critical role in preventing MCMV-induced morbidity. Mechanistically, we show that indirect activation of lung NK cells via interleukin (IL)-12 and type 1 interferon (IFN) inflammatory cytokines is dispensable, while direct activation via Ly49H is essential in preventing morbidity from i.t. infection. Additionally, we did not find a significant role for ILC2 or tissue-resident NK (trNK) cells in the prevention of viral dissemination, and we did not observe an increase in the abundance of these cells. These findings uncover an unanticipated role for pulmonary cNK cells in preventing viral dissemination from infected lungs.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772414","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