Funkce CX3CR1+ migratorních dendritických buněk v mechanismech centrální tolerance

Březina, Jiří

Display of thousands of self-antigens in the thymus is fundamental for the establishment of central tolerance as its failure can lead to the development of autoimmunity. Medullary thymic epithelial cells (mTECs) and thymic dendritic cells (DCs) constitute essential populations of antigen presenting cells (APCs) which present these self-antigens to developing T cells. While mTECs produce and present antigens in self-autonomous manner, DCs can hijack mTEC-derived antigens by the process of cooperative antigen transfer (CAT). It is well found that CAT is essential for working central tolerance, however, the overall heterogeneity of thymic APCs participating in CAT remains unclear. Using transgenic mouse models and multicolor flow cytometry analysis, we determined that APCs involved in CAT are exclusively of CD11c+ phenotype. Within these cells, we identified previously unrecognized CX3CR1+ subset of migratory DCs (mDCs) exhibiting monocyte/macrophage markers. These CX3CR1+ mDCs are more efficient in CAT than their CX3CR1- counterparts and reveal robust antigen presenting properties with the capability to present CAT-acquired antigen. Genetic ablation of CX3CR1+ mDCs resulted in increased cellularity of CD8+ and CD4+ thymocytes, indicating importance of this mDC subset for negative selection of...

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