Patients with intracranial aneurysms presented defects in regulatory T cells, which were associated with impairment in Tim-3 upregulation
Autor: | Yun-He Luo, Guo-Feng Zhao, Hai-Feng Zhang, Ming-Guang Zhao, Guo-Biao Liang |
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Rok vydání: | 2018 |
Předmět: |
Adult
Male 0301 basic medicine Endothelium T cell Immunology chemical and pharmacologic phenomena Inflammation T-Lymphocytes Regulatory Extracellular matrix 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Humans Immunology and Allergy Medicine Hepatitis A Virus Cellular Receptor 2 Pharmacology business.industry FOXP3 Forkhead Transcription Factors Intracranial Aneurysm hemic and immune systems Middle Aged Up-Regulation 030104 developmental biology Cytokine stimulation medicine.anatomical_structure Cancer research Cytokines Female medicine.symptom business 030217 neurology & neurosurgery CD8 |
Zdroj: | International Immunopharmacology. 64:350-355 |
ISSN: | 1567-5769 |
DOI: | 10.1016/j.intimp.2018.09.020 |
Popis: | Pathogenic inflammation contributes to aneurysm formation by mediating the destruction of the endothelium and the extracellular matrix and promoting pathogenic proliferation of smooth muscle cells. In mouse models, tolerance-inducing T regulatory (Treg) cells could significantly reduce the incidence and severity of aneurysms. Hence, it should be investigated why in human intracranial aneurysm (IA) patients, Treg cells failed to provide protection against aneurysm formation. In this study, the frequency and function of Treg cells in IA patients were examined. The frequency of Foxp3+ Treg cells was significantly lower in IA patients than in healthy controls. This downregulation was only specific to the Treg subset of CD4+ T cells, as the frequency of total CD4+ T cell was increased in IA patients. Subsequently, we found that the expressions of Treg-associated molecules, including Foxp3, CTLA-4, TGF-β, and IL-10, were significantly lower in Foxp3+ Treg cells from IA patients than in Foxp3+ Treg cells from healthy controls. In both healthy controls and IA patients, Foxp3+ Treg cells were distinguished into a more potent Tim-3+ subset and a less potent Tim-3− subset. The Tim-3+ subset of Foxp3+ Treg cells was significantly reduced in IA patients. Signaling via IL-2, IL-7, IL-15 and IL-21 was shown to promote Tim-3 upregulation in CD4+ and CD8+ T cells. Interestingly, we found that Tim-3 could be upregulated in Treg cells via the same mechanism, but compared to the Treg cells from healthy controls, the Treg cells from IA patients presented defects in Tim-3 upregulation upon cytokine stimulation. Together, our results demonstrated that Foxp3+ Treg cells in IA patients presented reduced function, which was associated with a defect in Tim-3 upregulation. |
Databáze: | OpenAIRE |
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