Crucial contribution of thymic Sirpα+ conventional dendritic cells to central tolerance against blood-borne antigens in a CCR2-dependent manner
T Baba, Y Nakamoto, N Mukaida - The Journal of Immunology, 2009 - journals.aai.org
T Baba, Y Nakamoto, N Mukaida
The Journal of Immunology, 2009•journals.aai.orgThymic dendritic cells (DCs) as well as thymic epithelial cells are presumed to be major
sentinels in central tolerance by inducing the apoptosis of autoreactive T progenitor cells.
The thymic DC population is composed of heterogeneous subsets including CD11c+ B220+
plasmacytoid DCs, CD11c+ B220− CD8α+ signal regulatory protein α (Sirpα)− and CD11c+
B220− CD8α− Sirpα+ conventional DCs (cDCs). However, the distinctive role of each DC
subset remains undefined. We show herein that Sirpα+ cDCs, a minor subpopulation, was …
sentinels in central tolerance by inducing the apoptosis of autoreactive T progenitor cells.
The thymic DC population is composed of heterogeneous subsets including CD11c+ B220+
plasmacytoid DCs, CD11c+ B220− CD8α+ signal regulatory protein α (Sirpα)− and CD11c+
B220− CD8α− Sirpα+ conventional DCs (cDCs). However, the distinctive role of each DC
subset remains undefined. We show herein that Sirpα+ cDCs, a minor subpopulation, was …
Abstract
Thymic dendritic cells (DCs) as well as thymic epithelial cells are presumed to be major sentinels in central tolerance by inducing the apoptosis of autoreactive T progenitor cells. The thymic DC population is composed of heterogeneous subsets including CD11c+ B220+ plasmacytoid DCs, CD11c+ B220− CD8α+ signal regulatory protein α (Sirpα)− and CD11c+ B220− CD8α− Sirpα+ conventional DCs (cDCs). However, the distinctive role of each DC subset remains undefined. We show herein that Sirpα+ cDCs, a minor subpopulation, was disseminated in the thymic cortical area with some of them uniquely localized inside perivascular regions and nearby small vessels in the thymus. The Sirpα+ but not Sirpα− cDC subset can selectively capture blood-circulating Ags. Moreover, in CCR2-deficient mice, the thymic Sirpα+ cDC subset, but not other thymic cell components, was moderately decreased especially in the perivascular regions. Concomitantly, these mice exhibited a modest impairment in intrathymic negative selection against blood-borne Ags, with the reduced capacity to uptake blood-borne Ags. Given their intrathymic cortical localization, CD11c+ B220− CD8α− Sirpα+ cDCs can have a unique role in the development of central tolerance against circulating peripheral Ags, at least partially in a CCR2-dependent manner.
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