ImmunoHorizons最新文献_第8页

Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development. SARS-CoV-2 Spike 蛋白的免疫表位和通用疫苗开发的考虑因素。

ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2400003

Nicholas Magazine, Tianyi Zhang, Anang D Bungwon, Michael C McGee, Yingying Wu, Gianluca Veggiani, Weishan Huang

{"title":"Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development.","authors":"Nicholas Magazine, Tianyi Zhang, Anang D Bungwon, Michael C McGee, Yingying Wu, Gianluca Veggiani, Weishan Huang","doi":"10.4049/immunohorizons.2400003","DOIUrl":"10.4049/immunohorizons.2400003","url":null,"abstract":"Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable of evading prior immunity. The mutation and evolution of SARS-CoV-2 have created a demand for persistent efforts in vaccine development. SARS-CoV-2 Spike protein has been the primary target for COVID-19 vaccine development, but it is also the hotspot of mutations directly involved in host susceptibility and virus immune evasion. Our ability to predict emerging mutants and select conserved epitopes is critical for the development of a broadly neutralizing therapy or a universal vaccine. In this article, we review the general paradigm of immune responses to COVID-19 vaccines, highlighting the immunological epitopes of Spike protein that are likely associated with eliciting protective immunity resulting from vaccination in humans. Specifically, we analyze the structural and evolutionary characteristics of the SARS-CoV-2 Spike protein related to immune activation and function via the TLRs, B cells, and T cells. We aim to provide a comprehensive analysis of immune epitopes of Spike protein, thereby contributing to the development of new strategies for broad neutralization or universal vaccination.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 3","pages":"214-226"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998713","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

SARS-CoV-2 Vaccine-Elicited Immunity after B Cell Depletion in Multiple Sclerosis. 多发性硬化症 B 细胞耗竭后 SARS-CoV-2 疫苗激发的免疫力

ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300108

Ryan M Baxter, Berenice Cabrera-Martinez, Tusharkanti Ghosh, Cody Rester, Miguel Guerrero Moreno, Tyler L Borko, Sean Selva, Chelsie L Fleischer, Nicola Haakonsen, Ariana Mayher, Emily Bowhay, Courtney Evans, Todd M Miller, Leah Huey, Jennifer McWilliams, Adrie van Bokhoven, Kevin D Deane, Vijaya Knight, Kimberly R Jordan, Debashis Ghosh, Jared Klarquist, Ross M Kedl, Amanda L Piquet, Elena W Y Hsieh

{"title":"SARS-CoV-2 Vaccine-Elicited Immunity after B Cell Depletion in Multiple Sclerosis.","authors":"Ryan M Baxter, Berenice Cabrera-Martinez, Tusharkanti Ghosh, Cody Rester, Miguel Guerrero Moreno, Tyler L Borko, Sean Selva, Chelsie L Fleischer, Nicola Haakonsen, Ariana Mayher, Emily Bowhay, Courtney Evans, Todd M Miller, Leah Huey, Jennifer McWilliams, Adrie van Bokhoven, Kevin D Deane, Vijaya Knight, Kimberly R Jordan, Debashis Ghosh, Jared Klarquist, Ross M Kedl, Amanda L Piquet, Elena W Y Hsieh","doi":"10.4049/immunohorizons.2300108","DOIUrl":"10.4049/immunohorizons.2300108","url":null,"abstract":"The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 3","pages":"254-268"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121681","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

PD-1 Limits IL-2 Production and Thymic Regulatory T Cell Development. PD-1 限制 IL-2 的产生和胸腺调节性 T 细胞的发育

ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300079

Breanna Caruso, Benjamin R Weeder, Reid F Thompson, Amy E Moran

{"title":"PD-1 Limits IL-2 Production and Thymic Regulatory T Cell Development.","authors":"Breanna Caruso, Benjamin R Weeder, Reid F Thompson, Amy E Moran","doi":"10.4049/immunohorizons.2300079","DOIUrl":"10.4049/immunohorizons.2300079","url":null,"abstract":"Inhibitory proteins, such as programmed cell death protein 1 (PD-1), have been studied extensively in peripheral T cell responses to foreign Ags, self-Ags, and neoantigens. Notably, these proteins are first expressed during T cell development in the thymus. Reports suggest that PD-1 limits regulatory T cell (Treg) development, but the mechanism by which PD-1 exerts this function remains unknown. The present study expands the evaluation of murine PD-1 and its ligands in the thymus, demonstrating that some of the highest expressers of PD-1 and programmed death-ligand 1 are agonist selected cells. Surprisingly, we reveal a selective role for PD-1 in regulating the developmental niche only for Tregs because other agonist selected cell populations, such as NK T cells, remain unchanged. We also ruled out PD-1 as a regulator of proliferation or cell death of agonist selected Tregs and further demonstrated that PD-1-deficient Tregs have reduced TCR signaling. Unexpectedly, the data suggest that PD-1-deficient thymocytes produce elevated levels of IL-2, a Treg niche-limiting cytokine. Collectively, these data suggest a novel role for PD-1 in regulating IL-2 production and the concurrent agonist selection of murine thymic Tregs. This observation has implications for the use of checkpoint blockade in the context of cancer and infection.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 3","pages":"281-294"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320247","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

Erdr1 Drives Macrophage Programming via Dynamic Interplay with YAP1 and Mid1. Erdr1通过与YAP1和Mid1的动态相互作用驱动巨噬细胞编程

ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2400004

Yuhang Wang

{"title":"Erdr1 Drives Macrophage Programming via Dynamic Interplay with YAP1 and Mid1.","authors":"Yuhang Wang","doi":"10.4049/immunohorizons.2400004","DOIUrl":"10.4049/immunohorizons.2400004","url":null,"abstract":"Erythroid differentiation regulator 1 (Erdr1) is a stress-induced, widely expressed, highly conserved secreted factor found in both humans and mice. Erdr1 is linked with the Hippo-YAP1 signaling. Initially identified as an inducer of hemoglobin synthesis, Erdr1 emerged as a multifunctional protein, especially in immune cells. Although Erdr1 has been implicated in regulating T cells and NK cell function, its role in macrophage remains unclear. This study explored the function and mechanism of Erdr1 in macrophage inflammatory response. The data demonstrated that Erdr1 could promote anti-inflammatory cytokine production, a function that also has been reported by previous research. However, I found Erdr1 also could play a proinflammatory role. The function of Erdr1 in macrophages depends on its dose and cell density. I observed that Erdr1 expression was inhibited in M1 macrophages but was upregulated in M2 macrophages compared with unpolarized macrophages. I hypothesized that Erdr1 balances the inflammatory response by binding with distinct adaptors dependent on varying concentrations. Mechanistically, I demonstrated YAP1 and Mid1 as the two adaptor proteins of Erdr1. The Erdr1-YAP1 interaction promotes anti-inflammatory cytokine production when Erdr1 levels are elevated, whereas the Erdr1-Mid1 interaction induces proinflammatory cytokine production when Erdr1 levels are decreased. This study highlights the effects of Erdr1 on regulating cytokine production from polarized macrophages potentially by regulating YAP1 in the nonclassical Hippo pathway.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 2","pages":"198-213"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934694","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

Persistent B Cell-Derived MHC Class II Signaling Is Required for the Optimal Maintenance of Tissue-Resident Helper T Cells. 组织驻留辅助性 T 细胞的最佳维持需要持续的 B 细胞衍生 MHC II 类信号。

ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2300093

Young Min Son, In Su Cheon, Chaofan Li, Jie Sun

{"title":"Persistent B Cell-Derived MHC Class II Signaling Is Required for the Optimal Maintenance of Tissue-Resident Helper T Cells.","authors":"Young Min Son, In Su Cheon, Chaofan Li, Jie Sun","doi":"10.4049/immunohorizons.2300093","DOIUrl":"10.4049/immunohorizons.2300093","url":null,"abstract":"Emerging studies have identified the critical roles of tissue-resident memory CD8+ T (TRM) and B (BRM) cells in the protection against mucosal viral infections, but the underlying mechanisms regulating robust development of TRM and BRM cells remain incompletely understood. We have recently shown that tissue-resident helper CD4+ T (TRH) cells, developed following influenza virus infection, function to sustain the optimal maintenance of TRM and BRM cells at the mucosal surface. In this study, we have explored the cellular and molecular cues modulating lung TRH persistence after influenza infection in C57BL/6 mice. We found that TRH cells were colocalized in tertiary lymphoid structures (TLSs) with local B cells. Abolishing TLSs or the depletion of B cells impaired lung TRH cell numbers. Of note, we found that persistent TCR signaling is needed for the maintenance of TRH cells after the clearance of infectious influenza virus. Furthermore, selective ablation of B cell-derived MHC class II resulted in partial reduction of lung TRH cell number after influenza infection. Our findings suggest that the interaction between lung-resident TRH cells and B cells, along with persistent Ag stimulation, is required to maintain TRH cells after respiratory viral infection.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 2","pages":"163-171"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725450","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

GSK3α/β Restrain IFN-γ-Inducible Costimulatory Molecule Expression in Alveolar Macrophages, Limiting CD4+ T Cell Activation. GSK3α/β 可抑制肺泡巨噬细胞中 IFN-γ 诱导性成本调控分子的表达，从而限制 CD4+ T 细胞的活化。

ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2300107

Laurisa M Ankley, Kayla N Conner, Taryn E Vielma, Jared J Godfrey, Mahima Thapa, Andrew J Olive

{"title":"GSK3α/β Restrain IFN-γ-Inducible Costimulatory Molecule Expression in Alveolar Macrophages, Limiting CD4+ T Cell Activation.","authors":"Laurisa M Ankley, Kayla N Conner, Taryn E Vielma, Jared J Godfrey, Mahima Thapa, Andrew J Olive","doi":"10.4049/immunohorizons.2300107","DOIUrl":"10.4049/immunohorizons.2300107","url":null,"abstract":"Macrophages play a crucial role in eliminating respiratory pathogens. Both pulmonary resident alveolar macrophages (AMs) and recruited macrophages contribute to detecting, responding to, and resolving infections in the lungs. Despite their distinct functions, it remains unclear how these macrophage subsets regulate their responses to infection, including how activation by the cytokine IFN-γ is regulated. This shortcoming prevents the development of therapeutics that effectively target distinct lung macrophage populations without exacerbating inflammation. We aimed to better understand the transcriptional regulation of resting and IFN-γ-activated cells using a new ex vivo model of AMs from mice, fetal liver-derived alveolar-like macrophages (FLAMs), and immortalized bone marrow-derived macrophages. Our findings reveal that IFN-γ robustly activates both macrophage types; however, the profile of activated IFN-γ-stimulated genes varies greatly between these cell types. Notably, FLAMs show limited expression of costimulatory markers essential for T cell activation upon stimulation with only IFN-γ. To understand cell type-specific differences, we examined how the inhibition of the regulatory kinases GSK3α/β alters the IFN-γ response. GSK3α/β controlled distinct IFN-γ responses, and in AM-like cells, we found that GSK3α/β restrained the induction of type I IFN and TNF, thus preventing the robust expression of costimulatory molecules and limiting CD4+ T cell activation. Together, these data suggest that the capacity of AMs to respond to IFN-γ is restricted in a GSK3α/β-dependent manner and that IFN-γ responses differ across distinct macrophage populations. These findings lay the groundwork to identify new therapeutic targets that activate protective pulmonary responses without driving deleterious inflammation.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 2","pages":"147-162"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725449","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

TCDD and CH223191 Alter T Cell Balance but Fail to Induce Anti-Inflammatory Response in Adult Lupus Mice. TCDD 和 CH223191 可改变 T 细胞平衡，但不能诱导成年狼疮小鼠的抗炎反应。

ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2300023

Fernando Gutierrez, Quiyana M Murphy, Brianna K Swartwout, Kaitlin A Read, Michael R Edwards, Leila Abdelhamid, Xavier Cabana-Puig, James C Testerman, Tian Xu, Ran Lu, Pavly Amin, Thomas E Cecere, Christopher M Reilly, Kenneth J Oestreich, Stanca M Ciupe, Xin M Luo

{"title":"TCDD and CH223191 Alter T Cell Balance but Fail to Induce Anti-Inflammatory Response in Adult Lupus Mice.","authors":"Fernando Gutierrez, Quiyana M Murphy, Brianna K Swartwout, Kaitlin A Read, Michael R Edwards, Leila Abdelhamid, Xavier Cabana-Puig, James C Testerman, Tian Xu, Ran Lu, Pavly Amin, Thomas E Cecere, Christopher M Reilly, Kenneth J Oestreich, Stanca M Ciupe, Xin M Luo","doi":"10.4049/immunohorizons.2300023","DOIUrl":"10.4049/immunohorizons.2300023","url":null,"abstract":"Aryl hydrocarbon receptor (AhR) responds to endogenous and exogenous ligands as a cytosolic receptor, transcription factor, and E3 ubiquitin ligase. Several studies support an anti-inflammatory effect of AhR activation. However, exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early stages of development results in an autoimmune phenotype and exacerbates lupus. The effects of TCDD on lupus in adults with pre-existing autoimmunity have not been described. We present novel evidence that AhR stimulation by TCDD alters T cell responses but fails to impact lupus-like disease using an adult mouse model. Interestingly, AhR antagonist CH223191 also changed T cell balance in our model. We next developed a conceptual framework for identifying cellular and molecular factors that contribute to physiological outcomes in lupus and created models that describe cytokine dynamics that were fed into a system of differential equations to predict the kinetics of T follicular helper (Tfh) and regulatory T (Treg) cell populations. The model predicted that Tfh cells expanded to larger values following TCDD exposure compared with vehicle and CH223191. Following the initial elevation, both Tfh and Treg cell populations continuously decayed over time. A function based on the ratio of predicted Treg/Tfh cells showed that Treg cells exceed Tfh cells in all groups, with TCDD and CH223191 showing lower Treg/Tfh cell ratios than the vehicle and that the ratio is relatively constant over time. We conclude that AhR ligands did not induce an anti-inflammatory response to attenuate autoimmunity in adult lupus mice. This study challenges the dogma that TCDD supports an immunosuppressive phenotype.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 2","pages":"172-181"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731250","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 Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs. 利用月经盘对女性下生殖道免疫细胞进行采样的无创方法

ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2300105

M Quinn Peters, Eva Domenjo-Vila, Marc Carlson, Blair Armistead, Paul T Edlefsen, Melanie Gasper, Smritee Dabee, Christopher Whidbey, Heather B Jaspan, Martin Prlic, Whitney E Harrington

{"title":"A Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs.","authors":"M Quinn Peters, Eva Domenjo-Vila, Marc Carlson, Blair Armistead, Paul T Edlefsen, Melanie Gasper, Smritee Dabee, Christopher Whidbey, Heather B Jaspan, Martin Prlic, Whitney E Harrington","doi":"10.4049/immunohorizons.2300105","DOIUrl":"10.4049/immunohorizons.2300105","url":null,"abstract":"T cells in the human female genital tract (FGT) are key mediators of susceptibility to and protection from infection, including HIV and other sexually transmitted infections. There is a critical need for increased understanding of the distribution and activation of T cell populations in the FGT, but current sampling methods require a healthcare provider and are expensive, limiting the ability to study these populations longitudinally. To address these challenges, we have developed a method to sample immune cells from the FGT utilizing disposable menstrual discs which are noninvasive, self-applied, and low in cost. To demonstrate reproducibility, we sampled the cervicovaginal fluid of healthy, reproductive-aged individuals using menstrual discs across 3 sequential days. Cervicovaginal fluid was processed for cervicovaginal cells, and high-parameter flow cytometry was used to characterize immune populations. We identified large numbers of live, CD45+ leukocytes, as well as distinct populations of T cells and B cells. Within the T cell compartment, activation and suppression status of T cell subsets were consistent with previous studies of the FGT utilizing current approaches, including identification of both tissue-resident and migratory populations. In addition, the T cell population structure was highly conserved across days within individuals but divergent across individuals. Our approach to sample immune cells in the FGT with menstrual discs will decrease barriers to participation and empower longitudinal sampling in future research studies.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 2","pages":"182-192"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934693","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

Phosphorylation of hnRNP A1-Serine 199 Is Not Required for T Cell Differentiation and Function. hnRNP A1-丝氨酸 199 的磷酸化不是 T 细胞分化和功能所必需的。

ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2300074

Tristan L A White, Ye Jin, Sean D A Roberts, Matthew J Gable, Penelope A Morel

{"title":"Phosphorylation of hnRNP A1-Serine 199 Is Not Required for T Cell Differentiation and Function.","authors":"Tristan L A White, Ye Jin, Sean D A Roberts, Matthew J Gable, Penelope A Morel","doi":"10.4049/immunohorizons.2300074","DOIUrl":"10.4049/immunohorizons.2300074","url":null,"abstract":"hnRNP A1 is an important RNA-binding protein that influences many stages of RNA processing, including transcription, alternative splicing, mRNA nuclear export, and RNA stability. However, the role of hnRNP A1 in immune cells, specifically CD4+ T cells, remains unclear. We previously showed that Akt phosphorylation of hnRNP A1 was dependent on TCR signal strength and was associated with Treg differentiation. To explore the impact of hnRNP A1 phosphorylation by Akt on CD4+ T cell differentiation, our laboratory generated a mutant mouse model, hnRNP A1-S199A (A1-MUT) in which the major Akt phosphorylation site on hnRNP A1 was mutated to alanine using CRISPR Cas9 technology. Immune profiling of A1-MUT mice revealed changes in the numbers of Tregs in the mesenteric lymph node. We found no significant differences in naive CD4+ T cell differentiation into Th1, Th2, Th17, or T regulatory cells (Tregs) in vitro. In vivo, Treg differentiation assays using OTII-A1-Mut CD4+ T cells exposed to OVA food revealed migration and homing defects in the A1-MUT but no change in Treg induction. A1-MUT mice were immunized with NP- keyhole limpet hemocyanin, and normal germinal center development, normal numbers of NP-specific B cells, and no change in Tfh numbers were observed. In conclusion, Akt phosphorylation of hnRNP A1 S199 does not play a role in CD4+ T cell fate or function in the models tested. This hnRNP A1-S199A mouse model should be a valuable tool to study the role of Akt phosphorylation of hnRNP A1-S199 in different cell types or other mouse models of human disease.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 2","pages":"136-146"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708871","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

Investigating the Antibody Imprinting Hypothesis among Canadian Paramedics after SARS-CoV-2 Omicron Variant Circulation. 调查 SARS-CoV-2 Omicron 变体传播后加拿大辅助医务人员的抗体印记假说。

ImmunoHorizons Pub Date : 2024-02-01 DOI: 10.4049/immunohorizons.2400010

Michael Asamoah-Boaheng, Brian Grunau, Mohammad Ehsanul Karim, Iryna Kayda, Justin Yap, Katherine Bessai, David M Goldfarb

引用次数: 0