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Glucocorticoids are steroid hormones with strong anti-inflammatory and immunosuppressive effects that are produced in a diurnal fashion. Although glucocorticoids have the potential to induce interleukin-7 receptor (IL-7R) expression in T cells, whether they control T cell homeostasis and responses at physiological concentrations remains unclear. We found that glucocorticoid receptor signaling induces IL-7R expression in mouse T cells by binding to an enhancer of the IL-7Rα locus, with a peak at midnight and a trough at midday. This diurnal induction of IL-7R supported the survival of T cells and their redistribution between lymph nodes, spleen, and blood by controlling expression of the chemokine receptor CXCR4. In mice, T cell accumulation in the spleen at night enhanced immune responses against soluble antigens and systemic bacterial infection. Our results reveal the immunoenhancing role of glucocorticoids in adaptive immunity and provide insight into how immune function is regulated by the diurnal rhythm.
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http://dx.doi.org/10.1016/j.immuni.2018.01.004 | DOI Listing |
Life Sci
August 2025
Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing, China. Electronic address:
Aims: Non-alcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction associated steatotic liver disease (MASLD), represents a spectrum of chronic liver diseases that eventually lead to cirrhosis and hepatocellular carcinoma. Liver fibrosis is both a pathological feature and a contributing factor in NAFLD. In the present study we investigated whether targeting pre-B cell leukemia transcription factor 1 (PBX1) and interleukin 7 receptor (IL7R) might ameliorate liver fibrosis in the context of NAFLD.
View Article and Find Full Text PDFFront Immunol
August 2025
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United States.
Introduction: Clinical studies of T cells engineered with chimeric antigen receptor (CAR) targeting CD19 in B-cell malignancies have demonstrated that relapse due to target antigen (CD19) loss or limited CAR T cell persistence is a common occurrence. The possibility of such events is greater in solid tumors, which typically display more heterogeneous antigen expression patterns and are known to directly suppress effector cell proliferation and persistence. T cell engineering strategies to overcome these barriers are being explored.
View Article and Find Full Text PDFJ Clin Immunol
August 2025
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
The interleukin-2 receptor γ (IL-2Rγ, or γc) is a crucial component of several cytokine receptor complexes. Deficiencies in γc lead to X-linked severe combined immunodeficiency (X-SCID), characterized by recurrent infections due to the absence or dysfunction of T and NK cells, and nonfunctional B cells. Missense variants in the γc extracellular region are linked to atypical X-SCID with normal counts of T, B, and NK cells and less severe symptoms, yet the underlying cellular and molecular mechanisms are not well understood.
View Article and Find Full Text PDFJ Immunother Cancer
July 2025
Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA
Background: Adoptive transfer of chimeric antigen receptor (CAR)-expressing natural killer (NK) cells has demonstrated success against hematological malignancies. Efficacy against solid tumors has been limited by poor NK cell survival and function in the suppressive tumor microenvironment (TME). To enhance efficacy against solid tumors, stimulatory cytokines have been incorporated into CAR-NK cell therapeutic approaches.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
Department of Protein Evolution, Max Planck Institute for Biology, 72076, Tübingen, Germany.
De novo design of binders capable of targeting arbitrarily selected epitopes remains a substantial challenge. Here, a generalizable computational strategy is presented to design site-specific protein binders, obviating steps of extensive empirical optimization or in vitro screening. The dock-and-design pipeline retrieves complementary scaffolds from a protein structure database to a given query epitope, where the scaffold is mutated to carve a binding site de novo.
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