Th17 and regulatory T lymphocytes in primary biliary cirrhosis and systemic sclerosis as models of autoimmune fibrotic diseases

Fenoglio, Daniela; Bernuzzi, Francesca; Battaglia, Florinda; Parodi, Alessia; Kalli, Francesca; Negrini, Simone; Palma, Raffaele De; Invernizzi, Pietro; Filaci, Gilberto

doi:10.1016/j.autrev.2012.05.004

Cited by 72 publications

(61 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One paper reported that the concentration of Th1-related IFN-γ was increased in PBC patients but decreased after UDCA treatment, indicating the relationship of this cytokine with disease activity (Saeki et al 1995). PBC also involves expression of TGF-β, which regulates the differentiation of Th17 cells and Tregs (Rosenbloom et al 2010;Fenoglio et al 2012;Liu et al 2013;Waluga et al 2015). The Th17-Treg balance is impaired in PBC (Fenoglio et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…PBC also involves expression of TGF-β, which regulates the differentiation of Th17 cells and Tregs (Rosenbloom et al 2010;Fenoglio et al 2012;Liu et al 2013;Waluga et al 2015). The Th17-Treg balance is impaired in PBC (Fenoglio et al 2012). Th17 cells mainly secrete IL-17, IL-6, and IL-23 and have been associated with the pathologies of several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis (RA), and inflammatory bowel disease (Miao et al 2014;Alunno et al 2015;Ueno et al 2015;Dos Passos et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…CD4+ T cells, including T helper type 1 (Th1) cells, type 17 (Th17) cells, and regulatory T cells (Tregs), are the main immune cells involved in the immunopathology of PBC (Fenoglio et al 2012;Webb et al 2015). Th1 cells mainly produce cytokines such as interferon gamma (IFN-γ), whereas Th17 cells mainly secrete IL-23, IL-17, IL-6, and others.…”

Section: Introductionmentioning

confidence: 99%

“…Th1 cells mainly produce cytokines such as interferon gamma (IFN-γ), whereas Th17 cells mainly secrete IL-23, IL-17, IL-6, and others. Tregs help regulate the body's immune system and prominently secrete immune molecules such as transforming growth factor beta (TGF-β) (Fenoglio et al 2012;Raphael et al 2015).…”

Section: Introductionmentioning

confidence: 99%

“…For example, biliary duct lesions in PBC patients showed elevated mRNA expression levels of IFN-γ (Shindo et al 1996). Fibrosisassociated cytokines, such as TGF-β (Rosenbloom et al 2010), contributed to the fibrotic process of PBC and affected the formation and function of Tregs and effector T lymphocytes (Th17 cells), which mainly produce interleukin (IL)-23, IL-6, and IL-17 (Fenoglio et al 2012). Tregs, which secrete TGF-β, play an important role in preventing autoimmune reactions (Filaci et al 2011;Yamaguchi et al 2011;Sakaguchi et al 2012).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Huang

Liu

et al. 2018

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological characteristics, such as progressive intrahepatic bile duct destruction, cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders. Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12 family of heterodimeric cytokines. IL-35 has immunosuppressive functions and plays an important role in many autoimmune diseases. In this study, we compared plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy individuals. The results showed that the relative expression levels of Ebi3 mRNA were lower in PBMCs from PBC patients than in PBMCs from healthy individuals, whereas the levels of p35 mRNA were similar in both groups. Plasma IL-35 concentrations were lower in patients with PBC than in healthy individuals. Plasma levels were higher in PBC patients at an advanced stage compared to patients at an early stage. Variable plasma levels with different stages were also found in transforming growth factor beta (TGF-β), which is mainly produced by regulatory T cells (Tregs). IL-35 and TGF-β levels were positively correlated with each other, and IL-35 was capable of promoting the inhibitory functions of Tregs in PBC patients at both the early and late stages of disease. Lower plasma IL-35 levels were accompanied by higher levels of typical clinical parameters, such as alkaline phosphatase, or of proinflammatory cytokines, such as interferon-gamma (IFN-γ), in PBC patients (P < 0.05 for each). We propose that IL-35 may be involved in the pathogenesis of PBC and could be a potential biomarker for diagnosing this disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Huang

Liu

et al. 2018

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

Important roles played by TGF‐β in hepatitis B infection

Karimi-Googheri

Daneshvar

Nosratabadi

et al. 2013

Journal of Medical Virology

View full text Add to dashboard Cite

Hepatitis B virus (HBV) which includes, fulminant, acute, chronic, asymptomatic, and occult HBV infection is the most prevalent virus that leads to human liver diseases. Chronic, asymptomatic, and occult infection can induce further sever diseases such as hepatocellular carcinoma (HCC) and cirrhosis of the liver. The underlying mechanisms that allow progression of the prolonged forms of the infection and subsequent HCC or cirrhosis of the liver are yet to be clarified. However, many researchers have suggested that immunological and genetic parameters may play important roles in the etiology of hepatitis B. Transforming growth factor beta (TGF-β) is an important cytokine with dual regulatory functions in the immune system and in the responses against viral infections. However, the pathways and mechanisms controlling these are not fully understood. The crucial roles of TGF-β in the development of Th17 and T regulatory lymphocytes, the main cell types involved in autoimmunity and destructive immune related diseases, have been documented and this provides insights into TGF-β function during hepatitis infection and subsequent HCC and cirrhosis of the liver. Recent findings also confirm that TGF-β directly alters hepatocyte function during hepatitis B, hence, the aim of this review is to address the current data regarding the association and status of TGF-β with hepatitis B infection and its related disorders including HCC and cirrhosis of the liver.

show abstract

Th17/Treg balance and factors related to autoimmune hepatitis

Xue

Feng

Yang

et al. 2022

Rheumatology & Autoimmunity

View full text Add to dashboard Cite

Background: Although Th17 cells and regulatory T cells play critical roles in autoimmune hepatitis, the balance between them in acute and chronic immune hepatitis is not well-studied. The objective of this study was to explore the role of Th17/Treg balance in autoimmune hepatitis. Methods: Thirty female Wistar rats were randomly divided into the following three groups: acute model (AC), chronic model (CC), and healthy control (HC). Aspartate aminotransferase, alanine aminotransferase, and bilirubin levels were measured. Peripheral blood interleukin (IL)-17, IL-6, IL-10, and transforming growth factor-β cytokine levels were also assessed. Flow cytometry was used to detect changes in the Th17 cell and Treg cell frequency, and the Th17/Treg ratio was calculated. Results: The frequency of Th17 cells and Treg cells were both increased (p < 0.05) and the Th17/Treg ratio was higher in the AC group compared with those in the HC group (p < 0.05). Th17 cell levels were significantly lower and Treg cell levels were significantly higher in the CC group, compared with those in the AC group (p < 0.05). In addition, the Th17/ Treg ratio was lower in the CC group compared with that in the HC group (p < 0.05). Conclusion:The Th17/Treg ratio was increased in the acute immune liver injury model and decreased in the chronic liver injury model. Th17/Treg imbalance may play a critical role in liver injury occurrence and development.K E Y W O R D S α-galcer, autoimmune hepatitis, ConA, Th17 cells, Treg cells Key points• Different liver damage caused by different modeling types will further explain the role of Th17/Treg imbalance in autoimmune hepatitis, and this imbalance has important implications for changes in immune status and disease progression. • In this study, α-galactosylceramide was used to establish the autoimmune hepatitis model, which shows similar pathological manifestations as that in human autoimmune hepatitis.

show abstract

Th17 and regulatory T lymphocytes in primary biliary cirrhosis and systemic sclerosis as models of autoimmune fibrotic diseases

Cited by 72 publications

References 66 publications

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Important roles played by TGF‐β in hepatitis B infection

Th17/Treg balance and factors related to autoimmune hepatitis

Contact Info

Product

Resources

About