Identification of a myeloid intrathymic pathway of dendritic cell development marked by expression of the granulocyte macrophage-colony-stimulating factor receptor.
In this study, the finding that a significant proportion of all dendritic cells (DCs) resident in vivo in the human postnatal thymus displayed a myeloid-related phenotype prompted us to re-examine the developmental origin of thymic DCs, a cell type hitherto considered to represent a homogeneous lymphoid-derived population. We show here that these novel intrathymic DCs are truly myeloid, as they arise from CD34(+) early thymic progenitors through CD34(lo) intermediates which have lost the capacity to generate T cells, but display myelomonocytic differentiation potential. We also demonstrate that phenotypically and functionally equivalent myeloid precursors devoid of T-cell potential do exist in vivo in the postnatal thymus. Moreover, although interleukin 7 (IL-7) supports the generation of such myeloid intermediates, we show that their developmental branching from the main intrathymic T-cell pathway is linked to the up-regulation of the myelomonocytic granulocyte macrophage-colony-stimulating factor (GM-CSF) receptor, to the down-regulation of the IL-7 receptor and to the lack of pre-T-cell receptor alpha (pTalpha) gene transcriptional activation. Taken together, these data challenge the current view that the thymus is colonized by a lymphoid-restricted progenitor and provide evidence that a more immature precursor population with lymphoid and myelomonocytic potential is actually seeding the human postnatal thymus.
de Yébenes
Virginia G
VG
Centro de Biología Molecular "Severo Ochoa," CSIC, Facultad de Biología, Universidad Autónoma de Madrid, Spain.
Carrasco
Yolanda R
YR
Ramiro
Almudena R
AR
Toribio
María L
ML
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D003713:Dendritic Cells / Q000166:cytology*; D005786:Gene Expression Regulation / Q000502:physiology; D019673:Genes, T-Cell Receptor alpha; D006801:Humans; D016130:Immunophenotyping; D023461:Myeloid Progenitor Cells / Q000166:cytology*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000502:physiology; D015533:Transcriptional Activation
D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D020395:Receptors, Interleukin-7