Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement

Nicola, Stefania; Rolla, Giovanni; Bucca, Caterina; Geronazzo, Giada; Ridolfi, Irene; Ferraris, Andrea; Fusaro, Enrico; Peroni, Clara Lisa; L, Dughera; Brussino, Luisa

doi:10.3390/cells9092106

Cited by 9 publications

(6 citation statements)

References 34 publications

(50 reference statements)

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“…Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by an extensive connective tissue involvement (1) along with a B-lymphocyte activation ( 14). Hashimoto's thyroiditis (HT) often occurs associated with SSc (7-9, 11, 12); several studies have focused on the immunological characteristics of isolated SSc or HT (13,15,18,(20)(21)(22)(23)(28)(29)(30), but it is unknown whether these two autoimmune disorders share some of the immunological mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Regulatory B Cells in Systemic Sclerosis Isolated or Concomitant With Hashimoto Thyroiditis

et al. 2022

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Systemic sclerosis (SSc) is a systemic autoimmune disease in which gastrointestinal disorders represent a complication in up to 90% of patients. SSc may associate with thyroid autoimmune disorders, with Hashimoto’s thyroiditis (HT) being the more prevalent worldwide. Previous studies have examined the behavior of Th17 lymphocytes and Breg cells in patients with HT and concomitant autoimmune organ-specific disorders. These immune phenotypes seem to play a significant role in the pathogenesis of both these autoimmune processes, but their behavior when these two disorders coexist has not been described. We analyzed Th17 and Breg (CD24hiCD38hi) cell subsets in 50 subjects (45F/5M; median age = 49 years): 18 were healthy donors (HD), 20 had isolated HT, and 12 had SSc, seven of whom had both HT and SSc. Breg cells’ function was also evaluated by measuring their IL-10 production when stimulated by specific activators. An increased percentage of Th17 lymphocytes characterized HT patients as compared to both HD and the whole group of SSc patients (p = 0.0018). On the contrary, the percentage of unstimulated Breg cells in SSc patients was higher (p = 0.0260), either associated or not with HT, as compared to both HT patients and HD, which, instead, showed a similar percentage of Breg cells. Following a specific stimulation with CpG, the percentages of Breg cells were increased in the whole sample of SSc patients (p < 0.001) as well as in isolated SSc and in SSc+HT ones as compared to isolated HT. However, qualitative analysis, obtained through the detection of the IL-10-producing phenotype, revealed that the percentage of CpG-stimulated CD24hiCD38hi-IL10+cells was significantly decreased in SSc patients (p < 0.0001) with no difference between isolated SSc and SSc+HT patients. The IL-10-producing phenotype was instead slightly increased in HT patients as compared to HD (4.1% vs. 2.8%). The presence of SSc seems to be characterized by an enrichment of total Breg cells but by a reduced Breg IL-10-producing phenotype, representing functional Bregs. This last finding was entirely due to the presence of SSc independently from the association with HT. This behavior is different from the ones described about the association of HT with organ-specific autoimmune disorders.

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Section: Discussionmentioning

confidence: 99%

Regulatory B Cells in Systemic Sclerosis Isolated or Concomitant With Hashimoto Thyroiditis

et al. 2022

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“…Any area of the gastrointestinal tract can be damaged, and the esophagus is particularly vulnerable ( 96 ). Nicola et al investigated the concentrations of Treg, Th17, and Th1-related cytokines in the digestive juices of SSc patients ( 97 ). They showed higher concentrations of IL-17A and lower concentrations of IL-10 and TGF-β in SSc patients with esophageal involvement.…”

Section: Imbalance Of Treg Cells and Th17 Cells In Sscmentioning

confidence: 99%

The Pathophysiological Roles of Regulatory T Cells in the Early Phase of Systemic Sclerosis

et al. 2022

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Systemic sclerosis (SSc) is an autoimmune disease that is characterized by vascular damage and fibrosis. Both clinical manifestations and immunological disturbances are diverse according to the disease duration. Particularly, changes in immunological processes are prominent in the early phase of SSc. The orchestration of several subsets of immune cells promotes autoimmune responses and inflammation, and eventually stimulates pro-fibrotic processes. Many reports have indicated that CD4+ T cells play pivotal roles in pathogenesis in the early phase of SSc. In particular, the pathogenic roles of regulatory T (Treg) cells have been investigated. Although the results were controversial, recent reports suggested an increase of Treg cells in the early phase of SSc patients. Treg cells secrete transforming growth factor-β (TGF-β), which promotes myofibroblast activation and fibrosis. In addition, the dysfunction of Treg cells in the early phase of SSc was reported, which results in the development of autoimmunity and inflammation. Notably, Treg cells have the plasticity to convert to T-helper17 (Th17) cells under pro-inflammatory conditions. Th17 cells secrete IL-17A, which could also promote myofibroblast transformation and fibrosis and contributes to vasculopathy, although the issue is still controversial. Our recent transcriptomic comparison between the early and late phases of SSc revealed a clear difference of gene expression patterns only in Treg cells. The gene signature of an activated Treg cell subpopulation was expanded in the early phase of SSc and the oxidative phosphorylation pathway was enhanced, which can promote Th17 differentiation. And this result was accompanied by the increase in Th17 cells frequency. Therefore, an imbalance between Treg and Th17 cells could also have an important role in the pathogenesis of the early phase of SSc. In this review, we outlined the roles of Treg cells in the early phase of SSc, summarizing the data of both human and mouse models. The contributions of Treg cells to autoimmunity, vasculopathy, and fibrosis were revealed, based on the dysfunction and imbalance of Treg cells. We also referred to the potential development in treatment strategies in SSc.

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“…Th17 lymphocytes are a branch of CD4 + helper T cells, and IL-17 is its main effector molecule. IL-17A expressed by Th17 cells can induce the production of chemokines in ESCC cells, such as CCL20, CXCL-9, CXCL-10, and CXCL13 ( 70 , 71 ). These chemokines could promote the proliferation and differentiation of Th17 lymphocytes in ESCC TME ( 72 ).…”

Section: The Role Of Tumor Microenvironment In Esophageal Squamous Ce...mentioning

confidence: 99%

The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma

2022

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Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, with a high rate of morbidity. The invasion and metastasis of ESCC is the main reason for high mortality. More and more evidence suggests that metastasized cancer cells require cellular elements that contribute to ESCC tumor microenvironment (TME) formation. TME contains many immune cells and stromal components, which are critical to epithelial–mesenchymal transition, immune escape, angiogenesis/lymphangiogenesis, metastasis niche formation, and invasion/metastasis. In this review, we will focus on the mechanism of different microenvironment cellular elements in ESCC invasion and metastasis and discuss recent therapeutic attempts to restore the tumor-suppressing function of cells within the TME. It will represent the whole picture of TME in the metastasis and invasion process of ESCC.

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Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement

Cited by 9 publications

References 34 publications

Regulatory B Cells in Systemic Sclerosis Isolated or Concomitant With Hashimoto Thyroiditis

Regulatory B Cells in Systemic Sclerosis Isolated or Concomitant With Hashimoto Thyroiditis

The Pathophysiological Roles of Regulatory T Cells in the Early Phase of Systemic Sclerosis

The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma

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