ImmunoHorizons最新文献_第5页

A Lower Dose of Infection Generates a Better Long-Term Immune Response against Toxoplasma gondii. 较低剂量的感染可产生更好的针对弓形虫的长期免疫反应。

ImmunoHorizons Pub Date : 2023-02-01 DOI: 10.4049/immunohorizons.2300006

Magali M Moretto, Jie Chen, Morgan Meador, Jasmine Phan, Imtiaz A Khan

{"title":"A Lower Dose of Infection Generates a Better Long-Term Immune Response against Toxoplasma gondii.","authors":"Magali M Moretto, Jie Chen, Morgan Meador, Jasmine Phan, Imtiaz A Khan","doi":"10.4049/immunohorizons.2300006","DOIUrl":"10.4049/immunohorizons.2300006","url":null,"abstract":"Toxoplasma gondii, an obligate intracellular pathogen, induces a strong immune response in the infected host. In the encephalitis model of infection, long-term protective immunity is mediated by CD8 T cells, with the CD4 T cell population providing important help. Most of the immune studies have used a 10- to 20-cyst dose of T. gondii, which leads to T cell dysfunctionality during the late phase of chronic infection and increases the chances of reactivation. In the current study, we compared the immune response of mice orally infected with either 2 or 10 cysts of T. gondii. During the acute phase, we demonstrate that the lower dose of infection generates a reduced number of CD4 and CD8 T cells, but the frequency of functional CD4 or CD8 T cells is similar in animals infected with two different doses. However, Ag-experienced T cells (both CD4 and CD8) are better maintained in lower dose-infected mice at 8 wk postinfection, with an increase number functional cells that exhibit lower multiple inhibitory receptor expression. In addition to better long-term T cell immunity, animals infected with a lower dose display reduced inflammation manifested by lesser Ag-specific T cell and cytokine responses during the very early stage of the acute infection. Our studies suggest a previously unappreciated role of dose-dependent early programming/imprinting of the long-term CD4/CD8 T cell response during T. gondii infection. These observations point to the need for an in-depth analysis of how early events shape long-term immunity against this pathogen.","PeriodicalId":13448,"journal":{"name":"ImmunoHorizons","volume":"7 2","pages":"177-190"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9668125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Polyamine Putrescine Is a Positive Regulator of Group 3 Innate Lymphocyte Activation. 多胺Putrescine是第3组天然淋巴细胞活化的正调节因子。

ImmunoHorizons Pub Date : 2023-01-01 DOI: 10.4049/immunohorizons.2200097

Prakash Sah, Lauren A Zenewicz

{"title":"The Polyamine Putrescine Is a Positive Regulator of Group 3 Innate Lymphocyte Activation.","authors":"Prakash Sah, Lauren A Zenewicz","doi":"10.4049/immunohorizons.2200097","DOIUrl":"10.4049/immunohorizons.2200097","url":null,"abstract":"Group 3 innate lymphocytes (ILC3s) rapidly respond to invading pathogens or inflammatory signals, which requires shifting cellular metabolic demands. Metabolic adaptations regulating ILC3 function are not completely understood. Polyamines are polycationic metabolites that have diverse roles in cellular functions and in immunity regulate immune cell biology, including Th17 cells. Whether polyamines play a role in ILC3 activation is unknown. In this article, we report that the polyamine synthesis pathway is important for ILC3 activation. IL-23-activated mouse ILC3s upregulate ornithine decarboxylase, the enzyme catalyzing the rate-limiting step of the conversion of ornithine to putrescine in polyamine synthesis, with a subsequent increase in putrescine levels. Inhibition of ornithine decarboxylase via a specific inhibitor, α-difluoromethylornithine, reduced levels of IL-22 produced by steady-state or IL-23-activated ILC3s in a putrescine-dependent manner. Thus, the polyamine putrescine is a positive regulator of ILC3 activation. Our results suggest that polyamines represent a potential target for therapeutic modulation of ILC3 activation during infection or inflammatory disorders.","PeriodicalId":13448,"journal":{"name":"ImmunoHorizons","volume":"7 1","pages":"41-48"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520894/pdf/nihms-1932402.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9266022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

CD19 Is Internalized Together with IgM in Proportion to B Cell Receptor Stimulation and Is Modulated by Phosphatidylinositol 3-Kinase in Bone Marrow Immature B Cells. 骨髓未成熟B细胞中CD19与IgM按比例内化并受磷脂酰肌醇3-激酶调节

ImmunoHorizons Pub Date : 2023-01-01 DOI: 10.4049/immunohorizons.2200092

Megan R McCaleb, Anjelica M Miranda, Kaysie C Ratliff, Raul M Torres, Roberta Pelanda

{"title":"CD19 Is Internalized Together with IgM in Proportion to B Cell Receptor Stimulation and Is Modulated by Phosphatidylinositol 3-Kinase in Bone Marrow Immature B Cells.","authors":"Megan R McCaleb, Anjelica M Miranda, Kaysie C Ratliff, Raul M Torres, Roberta Pelanda","doi":"10.4049/immunohorizons.2200092","DOIUrl":"10.4049/immunohorizons.2200092","url":null,"abstract":"Newly generated immature B cells that bind self-antigen with high avidity arrest in differentiation and undergo central tolerance via receptor editing and clonal deletion. These autoreactive immature B cells also express low surface levels of the coreceptor CD19, a key activator of the PI3K pathway. Signals emanating from both CD19 and PI3K are known to be critical for attenuating receptor editing and selecting immature B cells into the periphery. However, the mechanisms that modulate CD19 expression at this stage of B cell development have not yet been resolved. Using in vivo and in vitro models, we demonstrate that Cd19 de novo gene transcription and translation do not significantly contribute to the differences in CD19 surface expression in mouse autoreactive and nonautoreactive immature B cells. Instead, CD19 downregulation is induced by BCR stimulation in proportion to BCR engagement, and the remaining surface IgM and CD19 molecules promote intracellular PI3K-AKT activity in proportion to their level of expression. The internalized CD19 is degraded with IgM by the lysosome, but inhibiting lysosome-mediated protein degradation only slightly improves surface CD19. In fact, CD19 is restored only upon Ag removal. Our data also reveal that the PI3K-AKT pathway positively modulates CD19 surface expression in immature B cells via a mechanism that is independent of inhibition of FOXO1 and its role on Cd19 gene transcription while is dependent on mTORC1.","PeriodicalId":13448,"journal":{"name":"ImmunoHorizons","volume":"7 1","pages":"49-63"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9266648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypovitaminosis A Drives the Progression of Tubulointerstitial Lupus Nephritis through Potentiating Predisease Cellular Autoreactivity. 维生素A缺乏通过增强酶前细胞自身反应性来驱动管状间质性狼疮肾炎的进展。

ImmunoHorizons Pub Date : 2023-01-01 DOI: 10.4049/immunohorizons.2200015

Leila Abdelhamid, Razan Alajoleen, Kathryn M Kingsmore, Xavier Cabana-Puig, Ran Lu, Jing Zhu, James C Testerman, Yaqi Li, A Catharine Ross, Thomas E Cecere, Christopher M Reilly, Amrie C Grammer, Peter E Lipsky, Xin M Luo

{"title":"Hypovitaminosis A Drives the Progression of Tubulointerstitial Lupus Nephritis through Potentiating Predisease Cellular Autoreactivity.","authors":"Leila Abdelhamid, Razan Alajoleen, Kathryn M Kingsmore, Xavier Cabana-Puig, Ran Lu, Jing Zhu, James C Testerman, Yaqi Li, A Catharine Ross, Thomas E Cecere, Christopher M Reilly, Amrie C Grammer, Peter E Lipsky, Xin M Luo","doi":"10.4049/immunohorizons.2200015","DOIUrl":"10.4049/immunohorizons.2200015","url":null,"abstract":"Vitamin A (VA) deficiency (VAD) is observed in both humans and mice with lupus nephritis. However, whether VAD is a driving factor for accelerated progression of lupus nephritis is unclear. In this study, we investigated the effect of VAD on the progression of lupus nephritis in a lupus-prone mouse model, MRL/lpr. We initiated VAD either during gestation or after weaning to reveal a potential time-dependent effect. We found exacerbated lupus nephritis at ∼15 wk of age with both types of VAD that provoked tubulointerstitial nephritis leading to renal failure. This was concomitant with significantly higher mortality in all VAD mice. Importantly, restoration of VA levels after weaning reversed VAD-induced mortality. These results suggest VAD-driven acceleration of tubulointerstitial lupus nephritis. Mechanistically, at the earlier time point of 7 wk of age and before the onset of clinical lupus nephritis, continued VAD (from gestation until postweaning) enhanced plasma cell activation and augmented their autoantibody production, while also increasing the expansion of T lymphocytes that could promote plasma cell autoreactivity. Moreover, continued VAD increased the renal infiltration of plasmacytoid dendritic cells. VAD initiated after weaning, in contrast, showed modest effects on autoantibodies and renal plasmacytoid dendritic cells that were not statistically significant. Remarkably, analysis of gene expression in human kidney revealed that the retinoic acid pathway was decreased in the tubulointerstitial region of lupus nephritis, supporting our findings in MRL/lpr mice. Future studies will elucidate the underlying mechanisms of how VAD modulates cellular functions to exacerbate tubulointerstitial lupus nephritis.","PeriodicalId":13448,"journal":{"name":"ImmunoHorizons","volume":"7 1","pages":"17-29"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/22/ih2200015.PMC10563393.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9266024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dispensable Role of Aire in CD11c+ Conventional Dendritic Cells for Antigen Presentation and Shaping the Transcriptome. Aire在CD11c+常规树突状细胞中用于抗原呈递和形成转录组的可分配作用。

ImmunoHorizons Pub Date : 2023-01-01 DOI: 10.4049/immunohorizons.2200103

Ryuichiro Miyazawa, Jun-Ichi Nagao, Ken-Ichi Arita-Morioka, Minoru Matsumoto, Junko Morimoto, Masaki Yoshida, Takeshi Oya, Koichi Tsuneyama, Hideyuki Yoshida, Yoshihiko Tanaka, Mitsuru Matsumoto

{"title":"Dispensable Role of Aire in CD11c+ Conventional Dendritic Cells for Antigen Presentation and Shaping the Transcriptome.","authors":"Ryuichiro Miyazawa, Jun-Ichi Nagao, Ken-Ichi Arita-Morioka, Minoru Matsumoto, Junko Morimoto, Masaki Yoshida, Takeshi Oya, Koichi Tsuneyama, Hideyuki Yoshida, Yoshihiko Tanaka, Mitsuru Matsumoto","doi":"10.4049/immunohorizons.2200103","DOIUrl":"10.4049/immunohorizons.2200103","url":null,"abstract":"Abstract Aire, the defect of which is responsible for the development of autoimmunity, is predominantly expressed in medullary thymic epithelial cells, and it controls a wide variety of genes, including those of tissue-restricted Ags, for establishing thymic tolerance. Aire is also expressed from APCs in the periphery, called extrathymic Aire-expressing cells (eTACs), and their complementing role to thymic tolerance has been suggested. eTACs are composed of two distinct classes of APCs, conventional dendritic cell (cDC)–type and group 3 innate lymphoid cell (ILC3)-like–type expressing retinoic acid receptor–related orphan receptor γt (RORγt). Although the essential role of Aire in the latter in the Th17-mediated immune response against Candida albicans has been reported, the role of Aire in the cDC-type eTACs for this action has not been examined. Furthermore, the significance of Aire in the production of the transcriptome of the cDC-type eTACs remains unknown. We have approached these issues using a high-fidelity Aire-reporter mouse strain. We found that although the cDC-type eTACs dominated ILC3-like–type eTACs in number and they served as efficient APCs for the immune response against an exogenous Ag as well as for the C. albicans–specific Th17 immune response, loss of Aire in cDC-type eTACs showed no clear effect on these functions. Furthermore, loss of Aire showed no major impact on the transcriptome from cDC-type eTACs. These results suggested that Aire in cDC-type eTACs may not have a cell-intrinsic role in the immune response in contrast to the role of Aire in ILC3-like–type eTACs.","PeriodicalId":13448,"journal":{"name":"ImmunoHorizons","volume":"7 1","pages":"140-158"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/ae/ih2200103.PMC10563386.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10704029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats. 重组人血栓调节蛋白降低大鼠败血症性腹膜炎引起的死亡率和急性肺损伤。

ImmunoHorizons Pub Date : 2023-01-01 DOI: 10.4049/immunohorizons.2200094

Hiroshi Kono, Naohiro Hosomura, Hidetake Amemiya, Hiromichi Kawaida, Shinji Furuya, Katsutoshi Shoda, Hidenori Akaike, Yoshihiko Kawaguchi, Daisuke Ichikawa

{"title":"Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats.","authors":"Hiroshi Kono, Naohiro Hosomura, Hidetake Amemiya, Hiromichi Kawaida, Shinji Furuya, Katsutoshi Shoda, Hidenori Akaike, Yoshihiko Kawaguchi, Daisuke Ichikawa","doi":"10.4049/immunohorizons.2200094","DOIUrl":"10.4049/immunohorizons.2200094","url":null,"abstract":"This study aimed to investigate the therapeutic effects of recombinant human thrombomodulin (rhTM) on acute lung injury (ALI) caused by sepsis in rats. Rats that underwent cecal ligation and puncture (CLP) were treated with or without rhTM, and then mortality was analyzed. In another set of experiments, ALI was assessed. Furthermore, microthrombosis in the lungs was investigated by immunohistochemistry. Moreover, plasma inflammatory and anti-inflammatory cytokines, such as TNF-α, high-mobility group box chromosomal protein 1 (HMGB-1), and IL-10, were evaluated by ELISA. Production of TNF-α and HMGB-1 by isolated tissue macrophages (Mφs) was assessed in vitro. Mortality after CLP was significantly improved by rhTM treatment. In addition, rhTM treatment improved the wet/dry weight ratio of the lungs, the pulmonary microvascular permeability, and the lung injury scores in animals that underwent CLP. Microthrombosis was detected in the lungs after CLP. These pathophysiological changes were blunted by rhTM treatment. Increased plasma TNF-α and HMGB-1 levels were blunted by rhTM treatment; however, the anti-inflammatory cytokine IL-10 was significantly greater in the rhTM(+) group than in the rhTM(-) group. Increased TNF-α and HMGB-1 production by the tissue Mφs stimulated with LPS were significantly blunted by rhTM treatment in vitro, but the production of IL-10 by the tissue Mφs was not changed in the cells incubated with rhTM. Overall, rhTM improved the mortality caused by septic peritonitis. The possible mechanisms are most likely anti-inflammatory and anticoagulant effects, which lead to the prevention of ALI.","PeriodicalId":13448,"journal":{"name":"ImmunoHorizons","volume":"7 1","pages":"159-167"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/07/ih2200094.PMC10563402.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10772303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Relationship between Anti-SARS-CoV-2 S Abs and IFN-λ3 Levels in the Administration of Oxygen following COVID-19 Vaccination. 新冠肺炎疫苗接种后氧管理中抗SARS-CoV-2 S Abs和IFN-λ3水平的关系。

ImmunoHorizons Pub Date : 2023-01-01 DOI: 10.4049/immunohorizons.2200093

Yuichiro Takeshita, Yasuo To, Yusuke Kurosawa, Toru Kinouchi, Kota Tsuya, Yuji Tada, Kenji Tsushima

{"title":"Relationship between Anti-SARS-CoV-2 S Abs and IFN-λ3 Levels in the Administration of Oxygen following COVID-19 Vaccination.","authors":"Yuichiro Takeshita, Yasuo To, Yusuke Kurosawa, Toru Kinouchi, Kota Tsuya, Yuji Tada, Kenji Tsushima","doi":"10.4049/immunohorizons.2200093","DOIUrl":"10.4049/immunohorizons.2200093","url":null,"abstract":"Although the effectiveness of vaccination at preventing hospitalization and severe coronavirus disease (COVID-19) has been reported in numerous studies, the detailed mechanism of innate immunity occurring in host cells by breakthrough infection is unclear. One hundred forty-six patients were included in this study. To determine the effects of vaccination and past infection on innate immunity following SARS-CoV-2 infection, we analyzed the relationship between anti-SARS-CoV-2 S Abs and biomarkers associated with the deterioration of COVID-19 (IFN-λ3, C-reactive protein, lactate dehydrogenase, ferritin, procalcitonin, and D-dimer). Anti-S Abs were classified into two groups according to titer: high titer (≥250 U/ml) and low titer (<250 U/ml). A negative correlation was observed between anti-SARS-CoV-2 S Abs and IFN-λ3 levels (r = -0.437, p < 0.001). A low titer of anti-SARS-CoV-2 S Abs showed a significant association with oxygen demand in patients, excluding aspiration pneumonia. Finally, in a multivariate analysis, a low titer of anti-SARS-CoV-2 S Abs was an independent risk factor for oxygen demand, even after adjusting for age, sex, body mass index, aspiration pneumonia, and IFN-λ3 levels. In summary, measuring anti-SARS-CoV-2 S Abs and IFN-λ3 may have clinical significance for patients with COVID-19. To predict the oxygen demand of patients with COVID-19 after hospitalization, it is important to evaluate the computed tomography findings to determine whether the pneumonia is the result of COVID-19 or aspiration pneumonia.","PeriodicalId":13448,"journal":{"name":"ImmunoHorizons","volume":"7 1","pages":"97-105"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10704008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Humanized PD-1/PD-L1 Mouse Model Permits Direct Comparison of Antitumor Immunity Generated by Food and Drug Administration-Approved PD-1 and PD-L1 Inhibitors. 一种新的人源化PD-1/PD-L1小鼠模型可以直接比较食品和药物管理局批准的PD-1和PD-L1抑制剂产生的抗肿瘤免疫。

ImmunoHorizons Pub Date : 2023-01-01 DOI: 10.4049/immunohorizons.2200054

Whitney Barham, Michelle Hsu, Xin Liu, Susan M Harrington, Jacob B Hirdler, Joanina K Gicobi, Xingxing Zhu, Hu Zeng, Kevin D Pavelko, Yiyi Yan, Aaron S Mansfield, Haidong Dong

{"title":"A Novel Humanized PD-1/PD-L1 Mouse Model Permits Direct Comparison of Antitumor Immunity Generated by Food and Drug Administration-Approved PD-1 and PD-L1 Inhibitors.","authors":"Whitney Barham, Michelle Hsu, Xin Liu, Susan M Harrington, Jacob B Hirdler, Joanina K Gicobi, Xingxing Zhu, Hu Zeng, Kevin D Pavelko, Yiyi Yan, Aaron S Mansfield, Haidong Dong","doi":"10.4049/immunohorizons.2200054","DOIUrl":"10.4049/immunohorizons.2200054","url":null,"abstract":"Seven different anti-PD-1 and PD-L1 mAbs are now widely used in the United States to treat a variety of cancer types, but no clinical trials have compared them directly. Furthermore, because many of these Abs do not cross-react between mouse and human proteins, no preclinical models exist in which to consider these types of questions. Thus, we produced humanized PD-1 and PD-L1 mice in which the extracellular domains of both mouse PD-1 and PD-L1 were replaced with the corresponding human sequences. Using this new model, we sought to compare the strength of the immune response generated by Food and Drug Administration-approved Abs. To do this, we performed an in vivo T cell priming assay in which anti-PD-1/L1 therapies were given at the time of T cell priming against surrogate tumor Ag (OVA), followed by subsequent B16-OVA tumor challenge. Surprisingly, both control and Ab-treated mice formed an equally robust OVA-specific T cell response at the time of priming. Despite this, anti-PD-1/L1-treated mice exhibited significantly better tumor rejection versus controls, with avelumab generating the best protection. To determine what could be mediating this, we identified the increased production of CX3CR1+PD-1+CD8+ cytotoxic T cells in the avelumab-treated mice, the same phenotype of effector T cells known to increase in clinical responders to PD-1/L1 therapy. Thus, our model permits the direct comparison of Food and Drug Administration-approved anti-PD-1/L1 mAbs and further correlates successful tumor rejection with the level of CX3CR1+PD-1+CD8 + T cells, making this model a critical tool for optimizing and better utilizing anti-PD-1/L1 therapeutics.","PeriodicalId":13448,"journal":{"name":"ImmunoHorizons","volume":"7 1","pages":"125-139"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106088/pdf/nihms-1890023.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KIR Allelic Variation and the Remission of Atopic Dermatitis Over Time. KIR等位基因变异与特应性皮炎的缓解。

ImmunoHorizons Pub Date : 2023-01-01 DOI: 10.4049/immunohorizons.2200095

David J Margolis, Nandita Mitra, Ole J Hoffstad, Abha Chopra, Elizabeth J Phillips

{"title":"KIR Allelic Variation and the Remission of Atopic Dermatitis Over Time.","authors":"David J Margolis, Nandita Mitra, Ole J Hoffstad, Abha Chopra, Elizabeth J Phillips","doi":"10.4049/immunohorizons.2200095","DOIUrl":"10.4049/immunohorizons.2200095","url":null,"abstract":"Atopic dermatitis (AD) is a common chronic skin disease. Although generally thought to be a disease of T-cell dysregulation, recent studies have suggested that immune dysregulation of NK cells is also important. Killer cell Ig-like receptors (KIRs) are involved with NK cell regulation. The Pediatric Eczema Elective Registry is a U.S. nationwide longitudinal cohort with up to 10 y of follow-up in which 655 children had DNA available for full allelic KIR sequencing. Every 6 mo, AD activity was reported by Pediatric Eczema Elective Registry children. Using generalized estimating equations, we evaluated the association of KIR allelic variation in concert with known HLA binding ligands and whether the child reported AD in \"remission\" (no skin lesions and not using AD medication). KIR2DS4*001:01 (odds ratio 0.53, 95% CI [0.32, 0.88]) and KIR2DL4*001:02 (0.54, [0.33, 0.89]) in the presence of C*04:01 had the largest effect on decreasing the likelihood of AD remission. The haplotype KIR 2DL4*001:02 ∼ 2DS4*001:01 ∼ 3DL2*002:01 (0.77, [0.60, 0.99]) was also associated with a decreased likelihood of AD remission. Our findings add to the general body of evidence of a growing literature on the importance of NK cells with respect to the immunopathogenesis and natural history of AD.","PeriodicalId":13448,"journal":{"name":"ImmunoHorizons","volume":"7 1","pages":"30-40"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329861/pdf/nihms-1910846.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9766636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Elimination of 4T1 Mammary Tumor Cells by BALB/cBy UBC-GFP Transgenics following Stable Inheritance of the H-2b MHC Allele. H-2b MHC等位基因稳定遗传后通过BALB/cBy UBC-GFP转基因消除4T1哺乳动物肿瘤细胞。

ImmunoHorizons Pub Date : 2023-01-01 DOI: 10.4049/immunohorizons.2200101

Candice A Grzelak, Cyrus M Ghajar

引用次数: 0