THEMIS2 Impairs Antitumor Activity of NK Cells by Suppressing Activating NK Receptor Signaling
In this study, we found that a scaffold protein, THEMIS2, inhibits activating NK receptor signaling. Overexpression of THEMIS2 attenuated the effector function of human NK cells, whereas knockdown of THEMIS2 enhanced it. Mechanistically, THEMIS2 binds to GRB2 and phosphorylated SHP-1 and SHP-2 at the proximity of activating NK receptors DNAM-1 and NKG2D. Knockdown of THEMIS2 in primary human NK cells promoted the effector functions. Furthermore, Themis2-deficient mice showed low metastatic burden in an NK cell-dependent manner. These findings demonstrate that THEMIS2 has an inhibitory role in the antitumor activity of NK c...
Source: Journal of Immunology - April 15, 2024 Category: Allergy & Immunology Authors: Elfira Amalia Deborah Tsukasa Nabekura Kazuko Shibuya Akira Shibuya Source Type: research
Cutting Edge: First Lung Infection Permanently Enlarges Lymph Nodes and Enhances New T Cell Responses
J Immunol. 2024 Apr 15:ji2400010. doi: 10.4049/jimmunol.2400010. Online ahead of print.ABSTRACTHumans experience frequent respiratory infections. Immunology and vaccinology studies in mice are typically performed in naive specific pathogen-free animals responding to their very first respiratory challenge. We found that the first respiratory infection induces lifelong enlargement of the lung-draining mediastinal lymph nodes (medLNs). Furthermore, infection-experienced medLNs supported better naive T cell surveillance and effector responses to new unrelated infections that exhibited more biased accumulation and memory establ...
Source: Journal of Immunology - April 15, 2024 Category: Allergy & Immunology Authors: J Michael Stolley Milcah C Scott Stephen D O'Flanagan Marco K ünzli Courtney A Matson Eyob Weyu Ryan A Langlois Vaiva Vezys David Masopust Source Type: research
Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
In this study, we show that human MAIT cells require exogenous iron, transported via CD71 for optimal metabolic activity in MAIT cells, including their production of ATP. We demonstrate that restricting iron availability by either chelating environmental iron or blocking CD71 on MAIT cells results in impaired cytokine production and proliferation. These data collectively highlight the importance of a CD71-iron axis for human MAIT cell metabolism and functionality, an axis that may have implications in conditions where iron availability is limited.PMID:38619286 | DOI:10.4049/jimmunol.2300649 (Source: Journal of Immunology)
Source: Journal of Immunology - April 15, 2024 Category: Allergy & Immunology Authors: Eimear K Ryan Christy Clutter Conor De Barra Benjamin J Jenkins Simon O'Shaughnessy Odhr án K Ryan Chloe McKenna Helen M Heneghan Fiona Walsh David K Finlay Linda V Sinclair Nicholas Jones Daniel T Leung Donal O'Shea Andrew E Hogan Source Type: research
Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection
J Immunol. 2024 Apr 15:ji2300355. doi: 10.4049/jimmunol.2300355. Online ahead of print.ABSTRACTIn response to acute infection, naive CD4+ T cells primarily differentiate into T helper 1 (Th1) or T follicular helper (Tfh) cells that play critical roles in orchestrating cellular or humoral arms of immunity, respectively. However, despite the well established role of T-bet and BCL-6 in driving Th1 and Tfh cell lineage commitment, respectively, whether additional transcriptional circuits also underlie the fate bifurcation of Th1 and Tfh cell subsets is not fully understood. In this article, we study how the transcriptional reg...
Source: Journal of Immunology - April 15, 2024 Category: Allergy & Immunology Authors: Christine Nguyen Matthew Kudek Ryan Zander Hongshen Niu Jian Shen Ashley Bauer Donia Alson Achia Khatun Yao Chen Jie Sun William Drobyski Brian T Edelson Weiguo Cui Source Type: research
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J Immunol. 2024 May 1;212(9):1395. doi: 10.4049/jimmunol.2490002.NO ABSTRACTPMID:38621194 | DOI:10.4049/jimmunol.2490002 (Source: Journal of Immunology)
Source: Journal of Immunology - April 15, 2024 Category: Allergy & Immunology Source Type: research
Regulation of Tumor Dendritic Cells by Programmed Cell Death 1 Pathways
J Immunol. 2024 May 1;212(9):1397-1405. doi: 10.4049/jimmunol.2300674.ABSTRACTThe advent of immune checkpoint blockade therapy has revolutionized cancer treatments and is partly responsible for the significant decline in cancer-related mortality observed during the last decade. Immune checkpoint inhibitors, such as anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1), have demonstrated remarkable clinical successes in a subset of cancer patients. However, a considerable proportion of patients remain refractory to immune checkpoint blockade, prompting the exploration of mechanisms of treatment resistan...
Source: Journal of Immunology - April 15, 2024 Category: Allergy & Immunology Authors: Keith L Knutson Source Type: research
Integrin αvβ3 Limits Cytokine Production by Plasmacytoid Dendritic Cells and Restricts TLR-Driven Autoimmunity
J Immunol. 2024 Apr 12:ji2300290. doi: 10.4049/jimmunol.2300290. Online ahead of print.ABSTRACTPlasmacytoid dendritic cells (pDCs) are strongly implicated as a major source of IFN-I in systemic lupus erythematosus (SLE), triggered through TLR-mediated recognition of nucleic acids released from dying cells. However, relatively little is known about how TLR signaling and IFN-I production are regulated in pDCs. In this article, we describe a role for integrin αvβ3 in regulating TLR responses and IFN-I production by pDCs in mouse models. We show that αv and β3-knockout pDCs produce more IFN-I and inflammatory cytokines tha...
Source: Journal of Immunology - April 12, 2024 Category: Allergy & Immunology Authors: Alina K Lorant Anna E Yoshida Emily A Gilbertson Talyn Chu Caroline Stefani Mridu Acharya Jessica A Hamerman Adam Lacy-Hulbert Source Type: research
Disruption of IFN γ, GZMB, PRF1, or LYST Results in Reduced Suppressive Function in Human CD8+ T Cells
In this study, we further investigated the importance of IFNγ-, GZMB-, PRF1-, and LYST-associated pathways in CD8+ T cell-mediated suppression. Using the CRISPR-Cas9 ribonucleoprotein transfection system, we first optimized efficient gene knockout while maintaining high viability in primary bulk human CD8+ T cells. Knockout was confirmed through quantitative real-time PCR assays in all cases, combined with flow cytometry where appropriate, as well as confirmation of insertions and/or deletions at genomic target sites. We observed that the knockout of IFNγ, GZMB, PRF1, or LYST, but not the knockout of IL4 or IL5, resulted...
Source: Journal of Immunology - April 12, 2024 Category: Allergy & Immunology Authors: Chakrapani Vemulawada Pranav S Renavikar Michael P Crawford Scott Steward-Tharp Nitin J Karandikar Source Type: research
Integrin αvβ3 Limits Cytokine Production by Plasmacytoid Dendritic Cells and Restricts TLR-Driven Autoimmunity
J Immunol. 2024 Apr 12:ji2300290. doi: 10.4049/jimmunol.2300290. Online ahead of print.ABSTRACTPlasmacytoid dendritic cells (pDCs) are strongly implicated as a major source of IFN-I in systemic lupus erythematosus (SLE), triggered through TLR-mediated recognition of nucleic acids released from dying cells. However, relatively little is known about how TLR signaling and IFN-I production are regulated in pDCs. In this article, we describe a role for integrin αvβ3 in regulating TLR responses and IFN-I production by pDCs in mouse models. We show that αv and β3-knockout pDCs produce more IFN-I and inflammatory cytokines tha...
Source: Journal of Immunology - April 12, 2024 Category: Allergy & Immunology Authors: Alina K Lorant Anna E Yoshida Emily A Gilbertson Talyn Chu Caroline Stefani Mridu Acharya Jessica A Hamerman Adam Lacy-Hulbert Source Type: research
Disruption of IFN γ, GZMB, PRF1, or LYST Results in Reduced Suppressive Function in Human CD8+ T Cells
In this study, we further investigated the importance of IFNγ-, GZMB-, PRF1-, and LYST-associated pathways in CD8+ T cell-mediated suppression. Using the CRISPR-Cas9 ribonucleoprotein transfection system, we first optimized efficient gene knockout while maintaining high viability in primary bulk human CD8+ T cells. Knockout was confirmed through quantitative real-time PCR assays in all cases, combined with flow cytometry where appropriate, as well as confirmation of insertions and/or deletions at genomic target sites. We observed that the knockout of IFNγ, GZMB, PRF1, or LYST, but not the knockout of IL4 or IL5, resulted...
Source: Journal of Immunology - April 12, 2024 Category: Allergy & Immunology Authors: Chakrapani Vemulawada Pranav S Renavikar Michael P Crawford Scott Steward-Tharp Nitin J Karandikar Source Type: research
Integrin αvβ3 Limits Cytokine Production by Plasmacytoid Dendritic Cells and Restricts TLR-Driven Autoimmunity
J Immunol. 2024 Apr 12:ji2300290. doi: 10.4049/jimmunol.2300290. Online ahead of print.ABSTRACTPlasmacytoid dendritic cells (pDCs) are strongly implicated as a major source of IFN-I in systemic lupus erythematosus (SLE), triggered through TLR-mediated recognition of nucleic acids released from dying cells. However, relatively little is known about how TLR signaling and IFN-I production are regulated in pDCs. In this article, we describe a role for integrin αvβ3 in regulating TLR responses and IFN-I production by pDCs in mouse models. We show that αv and β3-knockout pDCs produce more IFN-I and inflammatory cytokines tha...
Source: Journal of Immunology - April 12, 2024 Category: Allergy & Immunology Authors: Alina K Lorant Anna E Yoshida Emily A Gilbertson Talyn Chu Caroline Stefani Mridu Acharya Jessica A Hamerman Adam Lacy-Hulbert Source Type: research
Disruption of IFN γ, GZMB, PRF1, or LYST Results in Reduced Suppressive Function in Human CD8+ T Cells
In this study, we further investigated the importance of IFNγ-, GZMB-, PRF1-, and LYST-associated pathways in CD8+ T cell-mediated suppression. Using the CRISPR-Cas9 ribonucleoprotein transfection system, we first optimized efficient gene knockout while maintaining high viability in primary bulk human CD8+ T cells. Knockout was confirmed through quantitative real-time PCR assays in all cases, combined with flow cytometry where appropriate, as well as confirmation of insertions and/or deletions at genomic target sites. We observed that the knockout of IFNγ, GZMB, PRF1, or LYST, but not the knockout of IL4 or IL5, resulted...
Source: Journal of Immunology - April 12, 2024 Category: Allergy & Immunology Authors: Chakrapani Vemulawada Pranav S Renavikar Michael P Crawford Scott Steward-Tharp Nitin J Karandikar Source Type: research
The Transcription Factor Zfp335 Promotes Differentiation and Survival of Effector Th1 Cells by Directly Regulating Lmna Expression
In this study, we elucidated the pivotal role of zinc finger protein 335 (Zfp335) in regulating effector Th1 cell differentiation and survival during acute bacterial infection. Mice with Zfp335 knockout in OT-II cells exhibited impaired Ag-specific CD4+ T cell expansion accompanied by a significant reduction in resistance to Listeria infection. Furthermore, Zfp335 deficiency restricted the effector CD4+ Th1 cell population and compromised their survival upon Listeria challenge. The expression of T-bet and IFN-γ was accordingly decreased in Zfp335-deficient Th1 cells. Mechanistically, Zfp335 directly bound to the promoter ...
Source: Journal of Immunology - April 10, 2024 Category: Allergy & Immunology Authors: Haiyan Liu Zhao Feng Anjun Jiao Linbo Lan Renyi Ding Wenhua Li Huiqiang Zheng Yanhong Su Xiaoxuan Jia Dan Zhang Xiaofeng Yang Lianjun Zhang Lina Sun Baojun Zhang Source Type: research
The Transcription Factor Zfp335 Promotes Differentiation and Survival of Effector Th1 Cells by Directly Regulating Lmna Expression
In this study, we elucidated the pivotal role of zinc finger protein 335 (Zfp335) in regulating effector Th1 cell differentiation and survival during acute bacterial infection. Mice with Zfp335 knockout in OT-II cells exhibited impaired Ag-specific CD4+ T cell expansion accompanied by a significant reduction in resistance to Listeria infection. Furthermore, Zfp335 deficiency restricted the effector CD4+ Th1 cell population and compromised their survival upon Listeria challenge. The expression of T-bet and IFN-γ was accordingly decreased in Zfp335-deficient Th1 cells. Mechanistically, Zfp335 directly bound to the promoter ...
Source: Journal of Immunology - April 10, 2024 Category: Allergy & Immunology Authors: Haiyan Liu Zhao Feng Anjun Jiao Linbo Lan Renyi Ding Wenhua Li Huiqiang Zheng Yanhong Su Xiaoxuan Jia Dan Zhang Xiaofeng Yang Lianjun Zhang Lina Sun Baojun Zhang Source Type: research
The Transcription Factor Zfp335 Promotes Differentiation and Survival of Effector Th1 Cells by Directly Regulating Lmna Expression
In this study, we elucidated the pivotal role of zinc finger protein 335 (Zfp335) in regulating effector Th1 cell differentiation and survival during acute bacterial infection. Mice with Zfp335 knockout in OT-II cells exhibited impaired Ag-specific CD4+ T cell expansion accompanied by a significant reduction in resistance to Listeria infection. Furthermore, Zfp335 deficiency restricted the effector CD4+ Th1 cell population and compromised their survival upon Listeria challenge. The expression of T-bet and IFN-γ was accordingly decreased in Zfp335-deficient Th1 cells. Mechanistically, Zfp335 directly bound to the promoter ...
Source: Journal of Immunology - April 10, 2024 Category: Allergy & Immunology Authors: Haiyan Liu Zhao Feng Anjun Jiao Linbo Lan Renyi Ding Wenhua Li Huiqiang Zheng Yanhong Su Xiaoxuan Jia Dan Zhang Xiaofeng Yang Lianjun Zhang Lina Sun Baojun Zhang Source Type: research
