| Autor: |
Zhong, Hui, Bao, Weili, Li, Xiaojuan, Miller, Allison, Seery, Caroline, Haq, Naznin, Bussel, James, Yazdanbakhsh, Karina |
| Zdroj: |
Blood; October 2012, Vol. 120 Issue: 16 p3326-3335, 10p |
| Abstrakt: |
Immune thrombocytopenia (ITP) results from decreased platelet production and accelerated platelet destruction. Impaired CD4+regulatory T-cell (Treg) compartment and skewed Th1 and possibly Th17 responses have been described in ITP patients. The trigger for aberrant T-cell polarization remains unknown. Because monocytes have a critical role in development and polarization of T-cell subsets, we explored the contribution of monocyte subsets in control of Treg and Th development in patients with ITP. Unlike circulating classic CD14hiCD16−subpopulation, the CD16+monocyte subset was expanded in ITP patients with low platelet counts on thrombopoietic agents and positively correlated with T-cell CD4+IFN-γ+levels, but negatively with circulating CD4+CD25hiFoxp3+and IL-17+Th cells. Using a coculture model, we found that CD16+ITP monocytes promoted the expansion of IFN-γ+CD4+cells and concomitantly inhibited the proliferation of Tregs and IL-17+Th cells. Th-1–polarizing cytokine IL-12, secreted after direct contact of patient T-cell and CD16+monocytes, was responsible for the inhibitory effect on Treg and IL-17+CD4+cell proliferation. Our findings are consistent with ITP CD16+monocytes promoting Th1 development, which in turn negatively regulates IL-17 and Treg induction. This underscores the critical role of CD16+monocytes in the generation of potentially pathogenic Th responses in ITP. |
| Databáze: |
Supplemental Index |
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