The results showed that Aire deficiency caused increased number of TFH cells both in vivo and in vitro. Further studies showed that Aire deficiency promoted TFH differentiation through the upregulation of ICOSL and IL-6 in DCs. Thus Aire could suppress the expression of ICOSL and IL-6 to inhibit TFH cell differentiation.
The results demonstrate that Aire expressed by bone marrow-derived dendritic cells plays an important role in the maintenance of homeostasis by regulating TRA expression and the differentiation of T cell subsets.
This study re-defines requirements for late stage intrathymic alphabetaT-cell development and demonstrates that Aire controls a CCR6-CCL20 axis that determines the developmental makeup of the intrathymic regulatory T-cell pool.
A mutation in LYN an inhibitory protein tyrosine kinase that is implicated in systemic autoimmunity combines with an Aire mutation to provoke organ-specific autoimmunity.
Our results identify Aire as an important regulator of peripheral T cell homeostasis in gastrointestinal tissues. Given a suitable trigger the absence of peripheral Aire leads to dysregulated T cell proliferation and disease.
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