Th17 and Treg Cells Innovate the Th1/Th2 Concept and Allergy Research

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.

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Sublingual immunotherapy for 4 years increased the number of Foxp3+ Treg cells, which correlated with clinical effects

Inflammation Research ◽

10.1007/s00011-021-01460-3 ◽

2021 ◽

Author(s):

Tetsuya Terada ◽

Masaya Matsuda ◽

Miki Inaba ◽

Junpei Hamaguchi ◽

Naoki Takemoto ◽

...

Keyword(s):

Sublingual Immunotherapy ◽

Treg Cells ◽

Clinical Effects

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Efficient IL-2R signaling differentially affects the stability, function, and composition of the regulatory T-cell pool

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00599-z ◽

2021 ◽

Author(s):

Marc Permanyer ◽

Berislav Bošnjak ◽

Silke Glage ◽

Michaela Friedrichsen ◽

Stefan Floess ◽

...

Keyword(s):

T Cell ◽

Treg Cell ◽

Cell Function ◽

Interleukin 2 ◽

Foxp3 Expression ◽

Treg Cells ◽

Receptor Expression ◽

Spontaneous Mutant ◽

Cell Pool ◽

And Function

AbstractSignaling via interleukin-2 receptor (IL-2R) is a requisite for regulatory T (Treg) cell identity and function. However, it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis, lineage stability and function in both resting and inflammatory conditions. Here, we characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25, the α-chain of IL-2R, which resulted in diminished receptor expression and reduced IL-2R signaling. Under noninflammatory conditions, Cd25Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune disease. In contrast, Cd25Y129H Treg cells failed to efficiently induce immune suppression and lost lineage commitment in a T-cell transfer colitis model, indicating that unimpaired IL-2R signaling is critical for Treg cell function in inflammatory environments. Moreover, single-cell RNA sequencing of Treg cells revealed that impaired IL-2R signaling profoundly affected the balance of central and effector Treg cell subsets. Thus, partial loss of IL-2R signaling differentially interferes with the maintenance, heterogeneity, and suppressive function of the Treg cell pool.

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Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-03018-y ◽

2021 ◽

Author(s):

Da Hyun Kang ◽

Chaeuk Chung ◽

Pureum Sun ◽

Da Hye Lee ◽

Song-I Lee ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Advanced Nsclc ◽

Checkpoint Inhibitors ◽

Standard Of Care ◽

Treg Cells ◽

University Hospital ◽

X Rays ◽

Lung Cancer Patients ◽

National University

Abstract Background Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. Methods This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. Results The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). Conclusion Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

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