T Cell Abnormalities in the Pathogenesis of Systemic Lupus Erythematosus: an Update

Chen, Ping-Min; Tsokos, George C.

doi:10.1007/s11926-020-00978-5

Cited by 69 publications

(56 citation statements)

References 90 publications

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“…Beside germinal center Tfh cells, various circulating Tfh-like populations and peripheral helper T (Tph) cells, expressing ICOS and producing IL-21, are now described. These cell populations resemble phenotypically Tfh cells but provoke autoantibody production outside of germinal centers [49]. Regarding ICOS − -Tresps which represent the largest subset within CD4 + -T-helper cells, we observed a strong decline of these cells within total CD4 + -T-helper cells in association with disease activity.…”

Section: Discussionmentioning

confidence: 64%

Impaired Differentiation of Highly Proliferative ICOS+-Tregs Is Involved in the Transition from Low to High Disease Activity in Systemic Lupus Erythematosus (SLE) Patients

Kälble

Lorenz

et al. 2021

IJMS

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Dysregulations in the differentiation of CD4+-regulatory-T-cells (Tregs) and CD4+-responder-T-cells (Tresps) are involved in the development of active systemic lupus erythematosus (SLE). Three differentiation pathways of highly proliferative inducible costimulatory molecule (ICOS)+- and less proliferative ICOS−-CD45RA+CD31+-recent-thymic-emigrant (RTE)-Tregs/Tresps via CD45RA−CD31+-memory-Tregs/Tresps (CD31+-memory-Tregs/Tresps), their direct proliferation via CD45RA+CD31−-mature naïve (MN)-Tregs/Tresps, and the production and differentiation of resting MN-Tregs/Tresp into CD45RA−CD31−-memory-Tregs/Tresps (CD31−-memory-Tregs/Tresps) were examined in 115 healthy controls, 96 SLE remission patients, and 20 active disease patients using six color flow cytometric analysis. In healthy controls an appropriate sequence of these pathways ensured regular age-dependent differentiation. In SLE patients, an age-independently exaggerated differentiation was observed for all Treg/Tresp subsets, where the increased conversion of resting MN-Tregs/Tresps particularly guaranteed the significantly increased ratios of ICOS+-Tregs/ICOS+-Tresps and ICOS−-Tregs/ICOS−-Tresps during remission. Changes in the differentiation of resting ICOS+-MN-Tresps and ICOS−-MN-Tregs from conversion to proliferation caused a significant shift in the ratio of ICOS+-Tregs/ICOS+-Tresps in favor of ICOS+-Tresps and a further increase in the ratio of ICOS−-Tregs/ICOS−-Tresps with active disease. The differentiation of ICOS+-RTE-Tregs/Tresps seems to be crucial for keeping patients in remission, where their limited production of proliferating resting MN-Tregs may be responsible for the occurrence of active disease flares.

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Section: Discussionmentioning

confidence: 64%

Impaired Differentiation of Highly Proliferative ICOS+-Tregs Is Involved in the Transition from Low to High Disease Activity in Systemic Lupus Erythematosus (SLE) Patients

Kälble

Lorenz

et al. 2021

IJMS

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“…Hemophagocytic lymphohistiocytosis(HLH), a disease linked to genetic defects in perforin mediated cytotoxicity, has been associated with impaired NK cells and increased proliferation of T cells [28] . Activated CD4 + T cells are involved in multiple aspects of SLE pathogenesis [1,23] . ICOS are vital markers of T cell activation and also essential costimulatory molecule to help B cell [23,29] .…”

Section: Discussionmentioning

confidence: 99%

“…Inducible T cell costimulator(ICOS) and programmed death 1(PD-1) are essential activation markers of CD4 + T cells for T-B-cell co-stimulation, which are key pathogenetic features of SLE [1,23] . Our study also con rmed that both ICOS%(5.24±5.04%, n=10 versus 1.36±0.64%, n=9, P<0.05) and PD-1%(18.3±8.13%, n=10 versus 8.71±4.65%, n=10, P<0.05) were higher in SLE patients than in HCs(Figure 6C).…”

Section: Attenuated Cytotoxicity and Altered Phenotypes Of Cd56 Dim Cd57 + Nk Cells In Sle Patientsmentioning

confidence: 99%

Increased Oxidative Stress Contributes to Impaired CD56dimCD57+ NK Cells in Patients With Systemic Lupus Erythematosus

Tian

Bai

et al. 2021

Preprint

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Background: Systemic lupus erythematosus(SLE) is characterized by loss of immune tolerance and imbalance of immune cell subsets. NK cells contribute to regulate both the innate and adaptive immune response. In this study, we aimed to detect peripheral NK cell subsets in SLE patients, investigate their cytotoxic effect on activated CD4+ T cells, and explore intrinsic mechanisms contributing to NK cell abnormality.Methods: Blood samples from healthy controls(HCs) and patients with SLE and rheumatoid arthritis(RA) were collected. The NK count, NK subsets(CD56bright , CD56dimCD57- , and CD56dimCD57+), phenotypes, along with apoptosis were analysed by flow cytometry. The t-stochastic neighbor embedding (tSNE) analysis of lymphocytes based on immune cells flow cytometry markers was performed. Mitochondrial reactive oxygen species(mtROS) and total ROS levels in NK cells were detected by MitoSOX Red and DCFH-DA staining respectively. Published data(GSE63829 and GSE23695) from Gene Expression Omnibus(GEO) was analyzed by Gene Set Enrichment Analysis(GSEA).Results: NK count was down-regulated in untreated SLE patients in comparison to untreated RA patients or HCs and the count was negatively correlated with disease activity. SLE patients exhibited a selective reduction in CD56dimCD57+ NK cell proportion, which was negatively correlated with Systemic Lupus Erythematosus Disease Activity Index(SLEDAI) and positively correlated with complement C3 and C4. CD56dimCD57+NK cells exhibited increased cytotoxic effect on activated CD4+ T cells relative to CD56dimCD57- NK cells. Compared with HCs, CD56dimCD57+ NK cells in SLE patients exhibited impaired cytotoxic function, increased apoptosis and higher levels of both mtROS and ROS. GSEA analysis indicated that ROS pathway was significantly enriched in NK cells from lupus. Compared with CD56dimCD57- NK cells in SLE patients, CD56dimCD57+ NK cells showed higher levels of oxidative stress and apoptosis. Furthermore, oxidative stress levels were negatively correlated with perforin expression and positively correlated with apoptosis. CD56dimCD57+ NK cells were more prone to undergo apoptosis when exposed to ROS in vitro. Conclusion: Beyond the reduced NK cell number, our study demonstrated a selective loss of mature CD56dimCD57+ NK cell subset, which was conversely correlated with disease activity. This subset showed attenuated cytotoxic function, up-regulated endogenous apoptosis and increased oxidative stress, which might contribute to NK cell abnormality.

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“…Нарушения врожденного и приобретенного иммунитета, характерные для СКВ, потенциально могут увеличивать риск инфицирования SARS-CoV-2, что характерно и для других вирусных инфекций [65,66], и предрасполагать к более тяжелому течению заболевания [67,68]. В предыдущих исследованиях была продемонстрирована важная роль вирусов Эпштейна -Барр, парвовируса В19, эндогенного ретровируса человека, в меньшей степени цитомегаловируса в развитии СКВ [66].…”

Section: скв и Covid-19unclassified

“…У афроамериканцев, страдающих СКВ, ЭФ-путь В-клеточного иммунного ответа ассоциируется с увеличением сывороточной концентрации анти-Sm и анти-RNP [108], а у пациентов с COVID-19 -с синтезом АНА (анти-Ro/SSA и анти-La/SSB). Другие общие иммунопатологические нарушения, характерные как для COVID-19, так и для СКВ, связаны с дефектами Т-регуляторных клеток и активацией Th17-типа иммунного ответа [109,110]. Все это вместе взятое может свидетельствовать о существовании «перекрещивающихся» механизмов иммунопатологии COVID-19 и СКВ, по крайней мере у некоторых пациентов, значение которых, однако, требует специальных исследований [111].…”

Section: скв и Covid-19unclassified

Problems of early diagnosis of systemic lupus erythematosus during the COVID-19 pandemic

Насонов

Попкова²,

Panafidina³

2021

Naučno-praktičeskaâ revmatologiâ

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Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unknown etiology, characterized by overproduction of organ-nonspecific autoantibodies to various components of the cell nucleus and cytoplasm and the development of immune-inflammatory damage to internal organs. The debut of SLE is preceded by an asymptomatic period, characterized by impaired immunological tolerance to its own autoantigens, determined by the multifaceted interaction of external, genetic and epigenetic factors, hormonal disorders, microbiome pathology, stress effects, etc. Development of a certain spectrum of clinical symptoms characteristic of SLE along with the detection of a reflects the progression of the immunopathological process in SLE, however, there is no generally accepted term that defines the patient’s condition, which has individual serological and clinical signs characteristic of this disease. In rheumatology, the concept of «incomplete» SLE is currently most often used. The problems of early diagnosis of SLE, clinical and laboratory predictors of the transformation of “incomplete” SLE into “reliable” SLE, difficulties in diagnosing SLE during the COVID-19 pandemic are considered. Particular attention is paid to the comparative characteristics of the immunopathological mechanisms of SLE and COVID-19.

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T Cell Abnormalities in the Pathogenesis of Systemic Lupus Erythematosus: an Update

Cited by 69 publications

References 90 publications

Impaired Differentiation of Highly Proliferative ICOS+-Tregs Is Involved in the Transition from Low to High Disease Activity in Systemic Lupus Erythematosus (SLE) Patients

Impaired Differentiation of Highly Proliferative ICOS+-Tregs Is Involved in the Transition from Low to High Disease Activity in Systemic Lupus Erythematosus (SLE) Patients

Increased Oxidative Stress Contributes to Impaired CD56dimCD57+ NK Cells in Patients With Systemic Lupus Erythematosus

Problems of early diagnosis of systemic lupus erythematosus during the COVID-19 pandemic

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