Lymphopenia in primary Sjögren’s syndrome is associated with premature aging of naïve CD4+ T cells

Fessler, Johannes; Fasching, Patrizia; Raicht, Andrea; Hammerl, Sabrina; Weber, Jennifer L.; Lackner, Angelika; Hermann, Josef; Dejaco, Christian; Graninger, Winfried; Schwinger, Wolfgang; Stradner, Martin

doi:10.1093/rheumatology/keaa105

Cited by 21 publications

(15 citation statements)

References 41 publications

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“…This phenomenon indicates that a common mechanism presented as lymphopenia may exist for the induction of autoimmunity. Of note, markers of immune aging have been documented in the ADs in humans [ 69 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 ] ( Table 1 ), such as reduced percentage of TREC + cells and/or lymphopenia, LIP in T cell subsets, and loss of CD28 + cells/accumulation of CD28 null cells in T cell subsets ( Table 1 ).…”

Section: Lymphopenia In Physiological and Autoimmune Conditionsmentioning

confidence: 99%

Lymphopenia, Lymphopenia-Induced Proliferation, and Autoimmunity

Sheu

Chiang

2021

IJMS

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Immune homeostasis is a tightly regulated system that is critical for defense against invasion by foreign pathogens and protection from self-reactivity for the survival of an individual. How the defects in this system might result in autoimmunity is discussed in this review. Reduced lymphocyte number, termed lymphopenia, can mediate lymphopenia-induced proliferation (LIP) to maintain peripheral lymphocyte numbers. LIP not only occurs in normal physiological conditions but also correlates with autoimmunity. Of note, lymphopenia is also a typical marker of immune aging, consistent with the fact that not only the autoimmunity increases in the elderly, but also autoimmune diseases (ADs) show characteristics of immune aging. Here, we discuss the types and rates of LIP in normal and autoimmune conditions, as well as the coronavirus disease 2019 in the context of LIP. Importantly, although the causative role of LIP has been demonstrated in the development of type 1 diabetes and rheumatoid arthritis, a two-hit model has suggested that the factors other than lymphopenia are required to mediate the loss of control over homeostasis to result in ADs. Interestingly, these factors may be, if not totally, related to the function/number of regulatory T cells which are key modulators to protect from self-reactivity. In this review, we summarize the important roles of lymphopenia/LIP and the Treg cells in various autoimmune conditions, thereby highlighting them as key therapeutic targets for autoimmunity treatments.

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Section: Lymphopenia In Physiological and Autoimmune Conditionsmentioning

confidence: 99%

Lymphopenia, Lymphopenia-Induced Proliferation, and Autoimmunity

Sheu

Chiang

2021

IJMS

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“…T cells comprise the helper T cell populations (CD4+), which differentiate in several subsets such as Th1, Th2, Th17, regulatory T cells (Treg), and T follicular helper cells (Tfh), as well as CD8+ T cells, also called Cytotoxic T Lymphocytes (CTL) [ 4 ]. Increased T cells infiltration into salivary glands (SG) from pSS patients has been evidenced accomplished by decreased levels in periphery blood, supporting the hypothesis that lymphopenia, a frequent finding in pSS patients associated with higher disease activity and increased mortality, might be owed to T cells migration [ 5 ].…”

Section: Introductionmentioning

confidence: 95%

T Cells Subsets in the Immunopathology and Treatment of Sjogren’s Syndrome

2020

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Sjogren’s syndrome (SS) is an autoimmune disease whose pathogenesis is characterized by an exacerbated T cell infiltration in exocrine glands, markedly associated to the inflammatory and detrimental features as well as the disease progression. Several helper T cell subsets sequentially converge at different stages of the ailment, becoming involved in specific pathologic roles. Initially, their activated phenotype endows them with high migratory properties and increased pro-inflammatory cytokine secretion in target tissues. Later, the accumulation of immunomodulatory T cells-derived factors, such as IL-17, IFN-γ, or IL-21, preserve the inflammatory environment. These effects favor strong B cell activation, instigating an extrafollicular antibody response in ectopic lymphoid structures mediated by T follicular helper cells (Tfh) and leading to disease progression. Additionally, the memory effector phenotype of CD8+ T cells present in SS patients suggests that the presence of auto-antigen restricted CD8+ T cells might trigger time-dependent and specific immune responses. Regarding the protective roles of traditional regulatory T cells (Treg), uncertain evidence shows decrease or invariable numbers of circulating and infiltrating cells. Nevertheless, an emerging Treg subset named follicular regulatory T cells (Tfr) seems to play a critical protective role owing to their deficiency that enhances SS development. In this review, the authors summarize the current knowledge of T cells subsets contribution to the SS immunopathology, focusing on the cellular and biomolecular properties allowing them to infiltrate and to harm target tissues, and that simultaneously make them key therapeutic targets for SS treatment.

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“…Vitali et al found that IFNG, TRIM26 , and EDN1 were overexpressed in pSS patients ( 12 ). Although studies have linked pSS to the immune system response in vivo ( 13 , 14 ), there is a lack of novel immune-related genes to study the underlying causes and inform treatment.…”

Section: Introductionmentioning

confidence: 99%

Novel Immune-Related Genetic Expression for Primary Sjögren's Syndrome

Cui

Wang

et al. 2022

Front. Med.

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Objective: To identify novel immune-related genes expressed in primary Sjögren's syndrome (pSS).Methods: Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened. The differences in immune cell proportion between normal and diseased tissues were compared, weighted gene co-expression network analysis was conducted to identify key modules, followed by a protein–protein interaction (PPI) network generation and enrichment analysis. The feature genes were screened and verified using the GEO datasets and quantitative real-time PCR (RT-qPCR).Results: A total of 345 DEGs were identified, and the proportions of gamma delta T cells, memory B cells, regulatory T cells (Tregs), and activated dendritic cells differed significantly between the control and pSS groups. The turquoise module indicated the highest correlation with pSS, and 252 key genes were identified. The PPI network of key genes showed that RPL9, RBX1, and RPL31 had a relatively higher degree. In addition, the key genes were mainly enriched in coronavirus disease-COVID-2019, hepatitis C, and influenza A. Fourteen feature genes were obtained using the support vector machine model, and two subtypes were identified. The genes in the two subtypes were mainly enriched in the JAK-STAT, p53, and toll-like receptor signaling pathways. The majority of the feature genes were upregulated in the pSS group, verified using the GEO datasets and RT-qPCR analysis.Conclusions: Memory B cells, gamma delta T cells, Tregs, activated dendritic cells, RPL9, RBX1, RPL31, and the feature genes possible play vital roles in the development of pSS.

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Lymphopenia in primary Sjögren’s syndrome is associated with premature aging of naïve CD4+ T cells

Cited by 21 publications

References 41 publications

Lymphopenia, Lymphopenia-Induced Proliferation, and Autoimmunity

Lymphopenia, Lymphopenia-Induced Proliferation, and Autoimmunity

T Cells Subsets in the Immunopathology and Treatment of Sjogren’s Syndrome

Novel Immune-Related Genetic Expression for Primary Sjögren's Syndrome

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