Elevated IL-6R on CD4+ T cells promotes IL-6 driven Th17 cell responses in patients with T1R leprosy reactions

Saini, Chaman; Srivastava, Rupesh K.; Tarique, Mohd; Kurra, Santosh; Khanna, Neena; Ramesh, V.; Sharma, Alpana

doi:10.1038/s41598-020-72148-7

Cited by 18 publications

(14 citation statements)

References 40 publications

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“…Cytokines function as key regulators of the differentiation of Th17 and Treg subsets, with IL-6 and TGF- β modulating the expression of lineage-specific transcription factors within CD4 + cells in the context of such fate determination [ 39 , 40 ]. Low TGF- β concentrations in the presence of IL-6 are able to drive the differentiation of Th17 cells and their consequent secretion of IL-17A and TNF- α , which in turn promote local inflammation, whereas high TGF- β concentrations are capable of promoting the differentiation of Tregs [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Fisetin on Allergic Contact Dermatitis via Regulating the Balance of Th17/Treg in Mice

Song

Shen

Zhang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Allergic contact dermatitis (ACD) is a form of chronic cutaneous inflammatory disease of immunological origin that has adverse impacts on patient quality of life, underscoring the need for the development of safe and effective therapeutic agents to treat affected individuals. Fisetin is a Chinese herbal preparation that reportedly exhibits antitumor, antioxidant, antimicrobial, anticoagulatory, and antimalarial activity. In the current report, the immunomodulatory activity of fisetin was appraised by assessing its impact on balance between regulatory T (Treg) and Th17 cells in an ACD model. Methods. BALB/c mice ( n = 60 ) were randomized into control, ACD model, CTX positive control (20 mg/kg), and fisetin treatment groups (three dose levels: 2, 4, or 8 mg/kg). ACD induction was achieved by sensitizing mice on the shaved ventral abdomen via the application of 5% DNFB (50 μL) on days 1 and 2, followed by rechallenge in the right ear with 5% DNFB (20 μL) on day 5. Beginning on day 1, immunized mice were intraperitoneally injected with the appropriate fisetin dose (in saline) once per day for 7 days. On day 7, ear swelling, transcription factor expression, Th17/Treg cell populations, and cytokine production were assessed in vivo. Results. Fisetin treatment significantly suppressed ear swelling and associated inflammatory cell infiltration, besides reducing the production of Th17 cytokines (IL-17, TNF-α, and IL-6) and the expression of the Th17 lineage transcription factor RORγt while simultaneously enhancing Treg-specific cytokine production (TGF-β and IL-10) and the expression of the Treg lineage transcription factor Foxp3, thereby restoring the Th17/Treg cell in ACD mice. Conclusions. These data indicate that fisetin exhibits immunomodulatory activity and can alter the Th17/Treg cell balance, highlighting its potential value as a treatment drug for ACD.

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Section: Discussionmentioning

confidence: 99%

Effects of Fisetin on Allergic Contact Dermatitis via Regulating the Balance of Th17/Treg in Mice

Song

Shen

Zhang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…11 IL-6R is expressed in Th17 cells and is necessary for retaining Th17-related transcriptional and functional profiles. 12,13 According to our data, IL-6Rα was differentially expressed on intratumoral Th17 cells, with one subpopulation expressing higher IL-6Rα and another subpopulation expressing relatively lower IL-6Rα. However, it is still unclear what caused this discrepancy in IL-6Rα expression.…”

Section: Discussionmentioning

confidence: 67%

Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model

Liu

Xiong

Wang

et al. 2021

Immunity Inflam & Disease

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Background: T helper 17 (Th17) cells actively participate in the tumor immune response in lung cancer. However, the heterogeneity and plasticity of intratumoral Th17 cells in lung cancer remain elusive. In this study, Th17 subpopulations were characterized in a mouse lung cancer model. Methods: Urethane was administered to induce lung cancer in interleukin (IL)-17-EGFP transgenic mice. Flow cytometry was used to analyze the phenotypes, signaling status, and functions of Th17 subpopulations either in vivo or in vitro. The adoptive transfer assay and real-time polymerase chain reaction were applied to analyze the plasticity of Th17 subpopulations. Results: IL-6Rα high CD27 − Th17 and IL-6Rα low CD27 + Th17 were identified in intratumoral Th17 cells. The two subpopulations expressed equivalent RORγt. However, the former expressed higher T-bet but lower Foxp3, more IL-17A and IFN-γ but less IL-10 than the latter. Furthermore, IL-6Rα high CD27 − Th17 moderately inhibited the proliferation of lung cancer cells while IL-6Rα low CD27 + Th17 could not. IL-6Rα high CD27 − Th17 exhibited weaker Jun N-terminal kinases (JNK) signaling but stronger signal transducer and activator of transcription 3 (Stat3) signaling than IL-6Rα low CD27 + Th17. The adoptive transfer assay indicated that both subpopulations downregulated RORγt in recipients' spleens but maintained RORγt in recipients' lungs. Meanwhile, IL-6Rα high CD27 − Th17 expressed higher T-bet and IFN-γ than IL-6Rα low CD27 + Th17 in the recipients. IL-6Rα low CD27 + Th17 expressed Foxp3 and IL-10 in recipients' spleens but not lungs.Conclusions: This study reveals intratumoral Th17 subpopulations with distinct functional properties and signaling patterns, thus offering valuable insight into Th17 heterogeneity and plasticity in lung cancer.

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“…Th17 cells secrete a range of inflammatory cytokines (IL-1, IL-17, TNF-α) that contribute to autoimmunity and associated tissue damage, with IL-17 playing a particularly central role in IL-17-mediated inflammatory exacerbation. Increases in IL-6 receptor expression on CD4 + T cells have recently been found to enhance Th17 cell-mediated inflammation by increasing IL-17 production in autoimmune contexts [ 33 ]. In experimental models of multiple sclerosis, high levels of IL-17 over observed proximal to CA1 hippocampal neurons [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Acupuncture regulates the Th17/Treg balance and improves cognitive deficits in a rat model of vascular dementia

Liu¹,

Pan²,

Zhenzhen³

et al. 2023

Heliyon

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Elevated IL-6R on CD4+ T cells promotes IL-6 driven Th17 cell responses in patients with T1R leprosy reactions

Cited by 18 publications

References 40 publications

Effects of Fisetin on Allergic Contact Dermatitis via Regulating the Balance of Th17/Treg in Mice

Effects of Fisetin on Allergic Contact Dermatitis via Regulating the Balance of Th17/Treg in Mice

Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model

Acupuncture regulates the Th17/Treg balance and improves cognitive deficits in a rat model of vascular dementia

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