The Role of B and T Lymphocyte Attenuator in Respiratory System Diseases

Deng, Zheng; Zheng, Yi; Cai, Pei; Zhang, Zheng

doi:10.3389/fimmu.2021.635623

Cited by 12 publications

(11 citation statements)

References 67 publications

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“…Lymphocytes have an important role in immune regulation and can be involved in the pathogenesis of respiratory diseases such as pneumonia, infections, asthma, and acute respiratory distress syndrome ( 62 ). The lower lymphocyte count in female mECT patients suggests that immunity may be reduced, potentially increasing the incidence of HAP.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in factors influencing hospital-acquired pneumonia in schizophrenia patients receiving modified electroconvulsive therapy

Yang

Yang²,

Liu³

et al. 2023

Front. Psychiatry

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BackgroundSex differences may be presented in the clinical features or symptoms of schizophrenia patients but also affect the occurrence of hospital-acquired pneumonia (HAP). Modified electroconvulsive therapy (mECT) is a common treatment method for schizophrenia, used in combination with antipsychotics. This retrospective research explores the sex difference in HAP affecting patients with schizophrenia who have received mECT treatment during hospitalization.MethodsWe included schizophrenia inpatients treated with mECT and antipsychotics between January 2015 and April 2022. Blood-related and demographic data collected on admission were analyzed. Influencing factors of HAP in male and female groups were assessed separately.ResultsA total of 951 schizophrenia patients treated with mECT were enrolled in the study, including 375 males and 576 females, of which 62 patients experienced HAP during hospitalization. The risk period of HAP in these patients was found to be the first day after each mECT treatment and the first three sessions of mECT treatment. Statistically significant differences in the incidence of HAP were identified in male vs. female groups, with an incidence in men about 2.3 times higher than that in women (P < 0.001). Lower total cholesterol (Z = −2.147, P = 0.032) and the use of anti-parkinsonian drugs (χ2 = 17.973, P < 0.001) were found to be independent risk factors of HAP in male patients, while lower lymphocyte count (Z = −2.408, P = 0.016), hypertension (χ2 = 9.096, P = 0.003), and use of sedative-hypnotic drugs (χ2 = 13.636, P < 0.001) were identified in female patients.ConclusionInfluencing factors of HAP in schizophrenia patients treated with mECT have gender differences. The first day after each mECT treatment and the first three sessions of mECT treatment were identified to have the greatest risk for HAP development. Therefore, it would be imperative to monitor clinical management and medications during this period according to these gender differences.

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Section: Discussionmentioning

confidence: 99%

Sex differences in factors influencing hospital-acquired pneumonia in schizophrenia patients receiving modified electroconvulsive therapy

Yang

Yang²,

Liu³

et al. 2023

Front. Psychiatry

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“…HVEM, which belongs to the tumor necrosis factor receptor (TNFR) superfamily, has been recognized as a novel immune checkpoint in recent years ( 33 ). HVEM is expressed primarily on immune cells and functions as a ligand to activate the B- and T-lymphocyte attenuator (BTLA) on other immune cells ( 34 ). Two categories of BTLA are CTLA-4/CD28/CD80/CD86 (function at the early phase of T-cell activation) and PD-1/PD-L1/PD-L2 (control the effector phase of the immune response in peripheral tissues) ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

“…on other immune cells (34). Two categories of BTLA are CTLA-4/CD28/CD80/CD86 (function at the early phase of T-cell activation) and PD-1/PD-L1/PD-L2 (control the effector phase of the immune response in peripheral tissues) (35).…”

Section: Discussionmentioning

confidence: 99%

Herpesvirus entry mediator on T cells as a protective factor for myasthenia gravis: A Mendelian randomization study

et al. 2022

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Background and objectivesMyasthenia gravis (MG) is a T cell-driven, autoantibody-mediated disorder affecting transmission in neuromuscular junctions. The associations between the peripheral T cells and MG have been extensively studied. However, they are mainly of observational nature, thus limiting our understanding of the effect of inflammatory biomarkers on MG risk. With large data sets now available, we used Mendelian randomization (MR) analysis to investigate whether the biomarkers on T cells are causally associated with MG and further validate the relationships.MethodsWe performed a two-sample MR analysis using genetic data from one genome-wide association study (GWAS) for 210 extensive T-cell traits in 3,757 general population individuals and the largest GWAS for MG currently available (1,873 patients versus 36,370 age/gender-matched controls) from US and Italy. Then the biomarkers of interest were validated separately in two GWASs for MG in FIN biobank (232 patients versus 217,056 controls) and UK biobank (152 patients versus 386,631 controls).ResultsIn the first analysis, three T-cell traits were identified to be causally protective for MG risk: 1) CD8 on terminally differentiated CD8+ T cells (OR [95% CI] = 0.71 [0.59, 0.86], P = 5.62e-04, adjusted P =2.81e-02); 2) CD4+ regulatory T proportion in T cells (OR [95% CI] = 0.44 [0.26, 0.72], P = 1.30e-03, adjusted P =2.81e-02); 3) HVEM expression on total T cells (OR [95% CI] = 0.67 [0.52, 0.86], P = 1.61e-03, adjusted P =2.81e-02) and other eight T-cell subtypes (e.g., naïve CD4+ T cells). In particular, HVEM is a novel immune checkpoint on T cells that has never been linked to MG before. The SNPs on the TNFRSF14 per se further support a more direct link between the HVEM and MG. The validation analysis replicated these results in both FIN and UK biobanks. Both datasets showed a concordant protective trend supporting the findings, albeit not significant.ConclusionThis study highlighted the role of HVEM on T cells as a novel molecular-modified factor for MG risk and validated the causality between T cells and MG. These findings may advance our understanding of MG’s immunopathology and facilitate the future development of predictive disease-relevant biomarkers.

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“…Herpesvirus entry mediator (HVEM) belongs to the tumor necrosis factor receptor (TNFR) superfamily and has been identified as the only BTLA ligand. BTLA and HVEM binding can help T cells maintain a naive state, thus inhibiting T-cell differentiation and proliferation and maintaining immune homeostasis (Deng et al, 2021;Flynn et al, 2013;Miller et al, 2009). Many studies on BTLA have produced similar conclusions.…”

Section: Introductionmentioning

confidence: 85%

PDGFR kinase inhibitor protects against septic death via regulation of BTLA

Wang

Deng

Sun

et al. 2022

Sci. China Life Sci.

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Sepsis, defined as life-threatening organ failure caused by a dysregulated host response to severe infection, is a major cause of death among intensive care unit patients. Therapies targeting on immunomodulatory is a new research field in sepsis treatment. B- and T-lymphocyte attenuator (BTLA) is an inhibitory costimulatory factor molecule of B and T lymphocytes. Studies have shown that elevated expression of BTLA in lymphocytes can reduce mortality in sepsis, but its regulatory compounds and the underlying mechanism remains to be elucidated. Here, we show that treatment with CP-673451 significantly decreases mortality of septic mouse. CP-673451 is a PDGFR kinase inhibitor which can promote the expression of BTLA, inhibit the release of chemokines such as CXCL13, and reduce first the chemotaxis of B cells to the peripheral blood and vital organs. CP-673451 also inhibits both the release of cytokines and chemokines such as IL-1β, IL-6, IL-10, TNF-α, CCL1, CCL2 and CCL7 and reduces both the chemotactic ability of T cells. This suggests that CP-673451 may prevent septic death by inhibiting lymphocyte chemotaxis and alleviating “cytokine storm”. In conclusion, our study provides a new therapeutic target and an effective compound for sepsis treatment. Supporting Information The supporting information is available online at 10.1007/s11427-021-2136-y. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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The Role of B and T Lymphocyte Attenuator in Respiratory System Diseases

Cited by 12 publications

References 67 publications

Sex differences in factors influencing hospital-acquired pneumonia in schizophrenia patients receiving modified electroconvulsive therapy

Sex differences in factors influencing hospital-acquired pneumonia in schizophrenia patients receiving modified electroconvulsive therapy

Herpesvirus entry mediator on T cells as a protective factor for myasthenia gravis: A Mendelian randomization study

PDGFR kinase inhibitor protects against septic death via regulation of BTLA

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