Aim: Systemic Lupus Erythematosus (SLE) patients display dysfunctions in T cell activation and anergy. Therefore the aims of our study were to explore the expression of anergy-related factors in CD4 T cells in relationship with regulatory T cells (Tregs) frequency in SLE patients and to identify strategies to redress these defects.
Method: Casitas B-cell lymphoma b (Cbl-b) and 'gene related to anergy in lymphocytes' (GRAIL) proteins were analyzed in peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy donors (HD) by immunoblotting. cbl-b, grail, growth response factors (egr)2 and egr3 messenger RNAs (mRNAs) were evaluated by real-time polymerase chain reaction in SLE and HD PBMCs and CD4 T cells. Phenotypic and functional characterization of CD4 T cells was performed by flow cytometry. Tregs expansion protocol consisted in culturing CD4 T cells for 14 or 21 days of experimental activation with anti-CD3 and anti-CD28 monoclonal antibodies, human recombinant interleukin (hrIL)-2, in the absence or presence of rapamycin (Rapa) or 1,25-(OH)2D3 (vitamin D: VitD).
Results: SLE PBMCs expressed low levels of Cbl-b and GRAIL proteins. Both SLE PBMCs and CD4 T cells expressed low levels of egr2/3 mRNAs. SLE patients had a reduced number of Tregs with impaired suppressive activity. An association between egr2 mRNA level in CD4 T cells and Tregs percentage was identified. Experimental activation of CD4 T cells in the presence of hrIL-2 and Rapa or VitD induced the expansion of SLE Tregs. However, on long-term, only Rapa exposure of SLE CD4 T cells yielded high numbers of Tregs with sustained suppressive activity.
Conclusion: Our results suggest a new strategy to correct defects in CD4 T cell tolerance mechanisms that may prove beneficial in SLE.
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http://dx.doi.org/10.1111/1756-185X.12509 | DOI Listing |
Sci Rep
December 2024
Department of Thyroid Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Although CCL17 has been reported to exert a vital role in many cancers, the related studies in the thyroid carcinoma have never reported. As a chemokine, CCL17 plays a positive role by promoting the infiltration of immune cells into the tumor microenviroment (TME) to influence tumor invasion and metastasis. Therefore, this study is aimed to investigate the association of CCL17 level with potential prognostic value on tumor immunity in the thyroid carcinoma (THCA) based on the bioinformatics analysis.
View Article and Find Full Text PDFNat Commun
December 2024
Division of Plastic Surgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Secondary lymphedema is a common sequel of oncologic surgery and presents a global health burden still lacking pharmacological treatment. The infiltration of the lymphedematous extremities with CD4T cells influences lymphedema onset and emerges as a promising therapy target. Here, we show that the modulation of CD4FOXP3CD25regulatory T (T) cells upon anti-CTLA4 treatment protects against lymphedema development in patients with melanoma and in a mouse lymphedema model.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
Dysregulated IL-10 producing regulatory B cells (Bregs) are associated with the progression of systemic lupus erythematosus. An immunomodulatory role of heat shock proteins (HSPs) is implicated in autoimmune diseases. However, the molecular basis underlying the role of Hspa13 in regulating Bregs function and lupus pathogenesis remains unclear.
View Article and Find Full Text PDFIndian J Med Res
November 2024
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, India.
Background & objectives The choice of anesthetic for better perioperative conservation of immune responses has always been contentious. This study investigated the differential impact of the intravenous anesthetic, propofol, and the volatile anesthetic, isoflurane on the T cell immune responses, if any, among individuals going through perioperative breast cancer. Methods Perioperative blood samples (preoperative, intraoperative and postoperative) collected from participants with breast cancer in two arms namely isoflurane arm (n=50) and the propofol arm (n=50) were analyzed for T cell immune response using flow cytometry and ELISA.
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