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TGF-β-mediated crosstalk between TIGIT Tregs and CD226CD8 T cells in the progression and remission of type 1 diabetes.
Nat Commun
October 2024
National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Article Synopsis
- Type 1 diabetes (T1D) is an autoimmune disease that leads to high blood sugar due to the destruction of insulin-producing cells, but sometimes patients experience a partial remission where blood sugar levels temporarily improve.
- Researchers conducted single-cell RNA sequencing to analyze immune cells in T1D patients at different stages and found changes in specific T cell subsets during the peri-remission phase.
- The study suggests that certain immune cells (TIGITCCR7 Tregs and CD226CCR7CD8 T cells) could act as biomarkers for β-cell function decline and may provide targets for new T1D treatments, as inhibiting one of these cell types showed benefits in mouse models of diabetes.
Critical roles of the miR-17∼92 family in thymocyte development, leukemogenesis, and autoimmunity.
Cell Rep
June 2024
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. Electronic address:
Article Synopsis
- Thymocyte development relies on the regulation of PI3K-Akt signaling to support cell growth and prevent diseases like leukemia and autoimmune disorders.
- Deleting the entire miR-17∼92 microRNA family significantly hinders thymocyte growth and reduces thymus cell numbers, while individual deletions show little effect; this is similar to the impact of depleting Dicer.
- The study indicates that miR-17∼92 promotes thymocyte proliferation by inhibiting Pten expression and suggests that targeting these microRNAs could be a strategy for treating leukemia and autoimmune conditions.
Publisher Correction: CD3ζ ITAMs enable ligand discrimination and antagonism by inhibiting TCR signaling in response to low-affinity peptides.
Nat Immunol
March 2024
Hematopoiesis and Lymphocyte Biology Section, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, USA.
CD3ζ ITAMs enable ligand discrimination and antagonism by inhibiting TCR signaling in response to low-affinity peptides.
Nat Immunol
December 2023
Hematopoiesis and Lymphocyte Biology Section, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, USA.
The T cell antigen receptor (TCR) contains ten immunoreceptor tyrosine-based activation motif (ITAM) signaling sequences distributed within six CD3 subunits; however, the reason for such structural complexity and multiplicity is unclear. Here we evaluated the effect of inactivating the three CD3ζ chain ITAMs on TCR signaling and T cell effector responses using a conditional 'switch' mouse model. Unexpectedly, we found that T cells expressing TCRs containing inactivated (non-signaling) CD3ζ ITAMs (6F-CD3ζ) exhibited reduced ability to discriminate between low- and high-affinity ligands, resulting in enhanced signaling and cytokine responses to low-affinity ligands because of a previously undetected inhibitory function of CD3ζ ITAMs.
View Article and Find Full Text PDFThemis2 regulates natural killer cell memory function and formation.
Nat Commun
November 2023
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki, 305-8575, Japan.
Immunological memory is a hallmark of the adaptive immune system. Although natural killer (NK) cells are innate immune cells important for the immediate host defence, they can differentiate into memory NK cells. The molecular mechanisms controlling this differentiation are yet to be fully elucidated.
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