Dysregulation of CD4+T Cell Subsets in Intracranial Aneurysm
| Autor: | Zhi-Qing Li, Wenxiu He, Guo-Biao Liang, Xu Gao, Chunyong Yu, Hai-Feng Zhang, Ming-Guang Zhao |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Receptors CCR6 Receptors CXCR3 medicine.medical_treatment T cell C-C chemokine receptor type 6 Biology CXCR3 Proinflammatory cytokine Interferon-gamma 03 medical and health sciences Chemokine receptor 0302 clinical medicine Genetics medicine Humans IL-2 receptor Molecular Biology Aged Tumor Necrosis Factor-alpha Interleukin-17 Autologous Monocytes Intracranial Aneurysm Cell Biology General Medicine Middle Aged Interleukin-10 Cytokine medicine.anatomical_structure Case-Control Studies Immunology Female 030217 neurology & neurosurgery 030215 immunology |
| Zdroj: | DNA and Cell Biology. 35:96-103 |
| ISSN: | 1557-7430 1044-5498 |
| DOI: | 10.1089/dna.2015.3105 |
| Popis: | Intracranial aneurysms (IAs) and potential IA rupture are one of the direct causes of permanent brain damage and mortality. Interestingly, the major risk factors of IA development, including hemodynamic stress, hypertension, smoking, and genetic predispositions, are closely associated with a proinflammatory immune status. Therefore, we examined the roles of CD4(+) T cells in IA pathogenesis. IA patients exhibited peripheral CD4(+) T-cell imbalance, with overrepresented T helper 1 (Th1) and Th17 activities and underrepresented Th2 and regulatory T (Treg) activities, including increased IFN-γ, TNF-α, and IL-17 production and decreased IL-10 production from total CD4(+) T cells. Chemokine receptors CXCR3 and CCR6 were used to identify Th1, Th2, and Th17 cell subsets, and CD4(+)CD25(hi) was used to identify Treg cells. Based on these markers, the data then showed altered cytokine production by each cell type and shifted subpopulation frequency. Moreover, this shift in frequency was directly correlated with IA severity. To examine the underlying mechanism of CD4(+) T cell skewing, we cocultured CD4(+) T cells with autologous monocytes and found that coculture with monocytes could significantly increase IFN-γ and IL-17 production through contact-independent mechanisms, demonstrating that monocytes could potentially contribute to the altered CD4(+) T cell composition in IA. Analyzing mRNA transcripts revealed significantly upregulated IL-1β and TNF-α expression by monocytes from IA patients. We found a loss of CD4(+) T cell subset balance that was likely to promote a higher state of inflammation in IA, which may exacerbate the disease through a positive feedback loop. |
| Databáze: | OpenAIRE |
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