Regulatory T cells demonstrate significantly increased functions following stimulation with IL-2 in a Tim-3-dependent manner in intracranial aneurysms
| Autor: | Yun-He Luo, Ming-Guang Zhao, Guo-Feng Zhao, Guo-Biao Liang, Hai-Feng Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Dependent manner T cell Immunology chemical and pharmacologic phenomena Inflammation Stimulation Tissue protection T-Lymphocytes Regulatory Treg cell 03 medical and health sciences Immune system Antigens CD Tissue damage medicine Humans Immunology and Allergy CTLA-4 Antigen Hepatitis A Virus Cellular Receptor 2 Aged Cell Proliferation Pharmacology Cumulus Cells Tumor Necrosis Factor-alpha Chemistry Intracranial Aneurysm hemic and immune systems Middle Aged Lymphocyte Activation Gene 3 Protein 030104 developmental biology medicine.anatomical_structure Cancer research Interleukin-2 Female Immunization medicine.symptom Signal Transduction |
| Zdroj: | International Immunopharmacology. 65:342-347 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2018.10.029 |
| Popis: | The formation of intracranial aneurysm (IA) is associated with the destruction of various cellular and structural components, which induces pathogenic inflammatory responses that further propagate tissue damage. The regulatory immune system can suppress exacerbated inflammation and offer tissue protection; however, previous studies by others and us have demonstrated that the regulatory T (Treg) cells were functionally impaired in IA patients. Hence, strategies that can improve Treg function in IA patients should be investigated. Based on our previous finding that IL-2 strongly elevated the expression of the checkpoint molecule Tim-3 in Treg cells, we examined the effect of IL-2 in the function of Treg cells from IA patients. External IL-2 significantly improved the proliferation of Treg cells, increased the expression of CTLA-4 and LAG-3, and enhanced Treg-mediated suppression of conventional T cell (Tconv) proliferation. Importantly, compared to the Tim-3- Treg cells, the Tim-3+ Treg cells presented comparable proliferation capacity, but significantly greater expressions of CTLA-4 and LAG-3 and significantly higher capacity to suppress Tconv proliferation. In addition, blocking Tim-3 abrogated IL-2-mediated enhancement of Tim-3+ Treg cells. We then investigated the IL-2 level in IA patients, and found that although IA patients and healthy controls presented similar serum IL-2 concentration, the concentrations of IL-1β and TNF-α were significantly higher in IA patients than in healthy controls, signaling a relative reduction in IL-2 abundance. Together, we found that IL-2 could significantly enhance the function of Treg cells from IA patients in a Tim-3-dependent manner. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect