Clinical relevance of RORγ positive and negative subsets of CD161<sup>+</sup>CD4<sup>+</sup>T cells in primary Sjögren’s syndrome

Zhao, Linlin; Nocturne, Gaëtane; Haskett, Scott; Boudaoud, Saida; Lazure, Thierry; Pajolec, Christine Le; Mariette, Xavier; Mingueneau, Michaël; Banerjee, Daliya

doi:10.1093/rheumatology/kew360

Cited by 14 publications

(13 citation statements)

References 44 publications

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“…Regarding TH17 cells involvement, both experimental and clinical data have pointed their crucial role in development and progression of SS by supporting autoreactive B cells responses. pSS patients show increased levels of circulating Th17 cells, as well as in salivary glands correlating with clinical parameter [ 48 , 49 ]. Th17 cells involvement in SS can be also analyzed by measuring their associated cytokines, particularly IL-17.…”

Section: Th1/th17 Cells: Primordial Effectors Coordinating the Infmentioning

confidence: 99%

“…Even though low evidence supporting this role until now, IL-17 has been described as a novel Th17 mechanism associated with the development of ELS in SS [ 54 ]. Th17 cells are more effective than Th1 cells in supporting B cells responses under autoimmunity conditions like SS, and an increased numbers of circulating RORγ+CD161+CD4+Th17 subset positively correlated with humoral manifestations [ 48 , 55 ]. IL-17 might contribute by modulating the immune response, since this cytokine induces secretion of inflammatory factors such as TNF, IL-6 and IL-1β and promotes immune cells recruitment by inducing secretion of chemokine like IL-8, CXCL9 and ligand for CCR3 receptors, as well as by modulating the integrity of epithelial barrier trough secretion of proteins like metalloproteinase [ 56 , 57 ].…”

Section: Th1/th17 Cells: Primordial Effectors Coordinating the Infmentioning

confidence: 99%

“…The dysregulated expression of the transcriptional co-activator TAZ (transcriptional coactivator with PDZ (postsynaptic density 65-discs large-zonula occludens 1binding)) leads to autoimmune diseases such as SS by promoting Th17 differentiation and Regarding TH17 cells involvement, both experimental and clinical data have pointed their crucial role in development and progression of SS by supporting autoreactive B cells responses. pSS patients show increased levels of circulating Th17 cells, as well as in salivary glands correlating with clinical parameter [48,49]. Th17 cells involvement in SS can be also analyzed by measuring their associated cytokines, particularly IL-17.…”

Section: Th1/th17 Cells: Primordial Effectors Coordinating the Inflammatory And Detrimental Environmentmentioning

confidence: 99%

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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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Section: Th1/th17 Cells: Primordial Effectors Coordinating the Infmentioning

confidence: 99%

Section: Th1/th17 Cells: Primordial Effectors Coordinating the Infmentioning

confidence: 99%

Section: Th1/th17 Cells: Primordial Effectors Coordinating the Inflammatory And Detrimental Environmentmentioning

confidence: 99%

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

2020

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“…They consist of mixed (serous and mucous) or only mucous acini and a ductal excretory system that is histologically different from that of the major salivary glands because of the absence of striated-type ducts within the labial salivary glands [1]. The labial salivary glands, which are readily accessible compared with other salivary glands, may be biopsied through normal-appearing mucosa in the endobuccal border of the lower lip after local anaesthesia [2]. Labial salivary gland biopsy is a simple surgical procedure and may be carried out on an ambulatory basis.…”

Section: Introductionmentioning

confidence: 99%

The unknown face of labial salivary glands. Labial salivary gland biopsy as a diagnostic tool

Kamiński¹,

Guzera²

2019

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Labial salivary gland biopsy (LSGB) is a minimally invasive and safe surgical procedure performed in the diagnosis and monitoring of selected diseases such as Sjögren's syndrome (SS), sarcoidosis, and amyloidosis. The aim of this study is to present the main possibilities and indications for the usefulness of LSGB in these diseases, their histopathological criteria, and the main advantages and limitations. Histopathological confirmation of SS is based on the presence of lymphocytic infiltrates, known as focal lymphocytic sialadenitis (FLS). FLS refers to the histopathological pattern of the presence of one or more foci in the biopsies, while the tissue surrounding the foci is composed mainly of unaffected parenchyma. A focus is defined as an aggregate of ≥ 50 lymphocytes, and the focus score (FS) is the total number of foci per 4 mm 2 of salivary gland tissue. FLS should be distinguished from other types of sialadenitis such as nonspecific chronic sialadenitis, sclerosing chronic sialadenitis, granulomatous inflammation, and lymphomas. Streszczenie Biopsja wargowych gruczołów ślinowych (LSGB) jest minimalnie inwazyjnym i bezpiecznym zabiegiem chirurgicznym wykorzystywanym w diagnostyce i monitorowaniu wybranych chorób, takich jak zespół Sjögrena (SS), sarkoidoza, amyloidoza. Celem pracy było przedstawienie głównych możliwości i wskazań do zastosowania LSGB, kryteriów histopatologicznych, głównych zalet i ograniczeń. Histopatologiczne potwierdzenie SS opiera się na stwierdzeniu obecności nacieków limfocytarnych znanych jako ogniskowe limfocytarne zapalenie gruczołów ślinowych (FLS). Nazwa FLS odnosi się histopatologicznie do obecności jednego lub więcej ognisk w biopsji, podczas gdy ognisko jest otoczone głównie przez niezmienioną tkankę miąższową. Ognisko jest definiowane jako skupisko 50 lub więcej limfocytów, a wynik jest liczbą ognisk przypadającą na 4 mm 2 tkanki gruczołowej. Ogniskowe limfocytarne zapalenie gruczołów ślinowych powinno być różnicowane z innymi typami zapalenia, takimi jak niespecyficzne zapalenie gruczołów ślinowych, twardniejące przewlekłe zapalenie gruczołów ślinowych, zapalenie ziarniniakowe i chłoniaki.

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“…These CD161-expressing T cells are considered important for antimicrobial immunity in humans ( 20 – 24 ). However, CD161-expressing T cells may also contribute to the development of various autoimmune diseases ( 25 – 28 ). CD161 is expressed by CD4 + T helper 17 (Th17) lineage cells and nonclassic T helper 1 (Th1) cells ( 18 , 29 – 31 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of Aging on the Frequency, Phenotype, and Function of CD161-Expressing T Cells

et al. 2018

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Immune-aging is associated with perturbed immune responses in the elderly. CD161-expressing T cells, i.e., the previously described subsets of CD161+ CD4+ T cells, CD161high CD8+ T cells, and CD161int CD8+ T cells, are highly functional, pro-inflammatory T cells. These CD161-expressing T cells are critical in immunity against microbes, while possibly contributing to autoimmune diseases. So far, little is known about the impact of aging on the frequency, phenotype, and function of these CD161-expressing T cells. In the current study, we investigated the impact of aging on CD161+ CD4+ T cells, CD161high CD8+ T cells, and CD161int CD8+ T cells in peripheral blood samples of 96 healthy subjects (age 20–84). Frequencies of CD161+ CD4+ T cells and CD161int CD8+ T cells were stable with aging, whereas frequencies of CD161high CD8+ T cells declined. Although CD161high CD8+ T cells were mostly T cell receptor-Vα7.2+ mucosal-associated invariant T cells, CD161 expressing CD4+ and CD8+ T cells showed a limited expression of markers for gamma–delta T cells or invariant natural killer (NK) T cells, in both young and old subjects. In essence, CD161-expressing T cells showed a similar memory phenotype in young and old subjects. The expression of the inhibitory NK receptor KLRG1 was decreased on CD161+ CD4+ T cells of old subjects, whereas the expression of other NK receptors by CD161-expressing T cells was unaltered with age. The expression of cytotoxic effector molecules was similar in CD161high and CD161int CD8+ T cells of young and old subjects. The ability to produce pro-inflammatory cytokines was preserved in CD161high and CD161int CD8+ T cells of old subjects. However, the percentages of IFN-γ+ and interleukin-17+ cells were significantly lower in CD161+ CD4+ T cells of old individuals than those of young individuals. In addition, aging was associated with a decrease of nonclassic T helper 1 cells, as indicated by decreased percentages of CD161-expressing cells within the IFN-γ+ CD4+ T cell compartment of old subjects. Taken together, aging is associated with a numerical decline of circulating CD161high CD8+ T cells, as well as a decreased production of pro-inflammatory cytokines by CD161+ CD4+ T cells. These aging-associated changes could contribute to perturbed immunity in the elderly.

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Clinical relevance of RORγ positive and negative subsets of CD161⁺CD4⁺T cells in primary Sjögren’s syndrome

Cited by 14 publications

References 44 publications

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

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

The unknown face of labial salivary glands. Labial salivary gland biopsy as a diagnostic tool

Impact of Aging on the Frequency, Phenotype, and Function of CD161-Expressing T Cells

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Clinical relevance of RORγ positive and negative subsets of CD161+CD4+T cells in primary Sjögren’s syndrome

Cited by 14 publications

References 44 publications

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

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

The unknown face of labial salivary glands. Labial salivary gland biopsy as a diagnostic tool

Impact of Aging on the Frequency, Phenotype, and Function of CD161-Expressing T Cells

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Product

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Clinical relevance of RORγ positive and negative subsets of CD161⁺CD4⁺T cells in primary Sjögren’s syndrome