Generalized vitiligo (GV) is characterized by white patches due to autoimmune loss of melanocytes. Regulatory T cells (Tregs) maintain immune homeostasis, while NK cells eliminate pathogens and tumors. Increased NK cell frequency and reduced Treg frequency and suppressive capacity are observed in vitiligo patients. However, studies assessing Treg-mediated suppression of NK cell functions in GV are lacking. Therefore, our study aimed to assess in vitro Treg-mediated suppression of NK cells function over K562 and SK-Mel-28 cells in 31 GV patients and 30 controls using the BrdU-cell proliferation assay. We found decreased Treg-mediated suppression of NK cell function in GV patients (p = 0.0289). Moreover, increased NK cell-mediated K562 and SK-Mel-28 cells' suppression was observed in GV patients (p = 0.0207,p = 0.0419). Disease activity-based analysis, suggested reduced Treg-mediated suppression of NK cell function and increased NK cell function in active vitiligo patients (p = 0.03,p = 0.0436). Interestingly, age-based analysis suggested decreased Treg-mediated suppression of NK cell function in 1-20 and 21-40 years age groups compared to 41-60 years age group of GV patients (p = 0.005,p = 0.0380). Overall, our study, for the first time, suggests that decreased Treg-mediated suppression of NK cells may lead to increased destruction of melanocytes in GV, and this knowledge may help in developing effective therapeutics based on Tregs and NK cells for GV.
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http://dx.doi.org/10.1016/j.humimm.2023.110737 | DOI Listing |
Nat Commun
January 2025
Infinity, Toulouse Institute for Infectious and Inflammatory Diseases, University of Toulouse, Inserm U1291, CNRS U5051, Toulouse, France.
Protective immune responses require close interactions between conventional (Tconv) and regulatory T cells (Treg). The extracellular mediators and signaling events that regulate the crosstalk between these CD4 T cell subsets have been extensively characterized. However, how Tconv translate Treg-dependent suppressive signals at the chromatin level remains largely unknown.
View Article and Find Full Text PDFJ Leukoc Biol
December 2024
School of Life Sciences, Arizona State University, Phoenix, AZ.
Regulatory T cells can suppress activated T cell proliferation by direct cell-contact, although the exact mechanism is poorly understood. Identification of a Treg-specific cell surface molecule that mediates suppression would offer a unique target for cancer immunotherapy to inhibit Treg immunosuppressive function or deplete Tregs in the tumor microenvironment. In this study, we explored a method of whole cell immunization using a Treg-like cell line (MoT cells) to generate and screen monoclonal antibodies that bound cell surface proteins in their native conformations and functionally reversed Treg-mediated suppression.
View Article and Find Full Text PDFJ Invest Dermatol
December 2024
Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Electronic address:
Exposure to UVB induces the expansion of regulatory T cells (Tregs) expressing proenkephalin and amphiregulin with a healing function in the skin. It is unclear how this UVB exposure affects the functionally distinct subsets of skin Tregs. In this study, we have demonstrated that skin-resident CD81Tregs expressing both proenkephalin gene Penk and amphiregulin gene Areg expanded after UVB irradiation.
View Article and Find Full Text PDFMol Cancer
December 2024
Department of Dental Materials, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, 110002, Liaoning, China.
Oral squamous cell carcinoma (OSCC) is a prevalent oral malignancy, which poses significant health risks with a high mortality rate. Regulatory T cells (Tregs), characterized by their immunosuppressive capabilities, are intricately linked to OSCC progression and patient outcomes. The metabolic reprogramming of Tregs within the OSCC tumor microenvironment (TME) underpins their function, with key pathways such as the tryptophan-kynurenine-aryl hydrocarbon receptor, PI3K-Akt-mTOR and nucleotide metabolism significantly contributing to their suppressive activities.
View Article and Find Full Text PDFCell Rep
November 2024
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address:
Regenerative medicine is a rapidly expanding field harnessing human pluripotent stem cell (hPSC)-derived cells and tissues to treat many diseases, including type 1 diabetes. However, graft immune protection remains a key challenge. Chimeric antigen receptor (CAR) technology confers new specificities to effector T cells and immunosuppressive regulatory T cells (Tregs).
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