1. Bone marrow-derived IL-13Rα1-positive thymic progenitors are restricted to the myeloid lineage.
- Author
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Haymaker CL, Guloglu FB, Cascio JA, Hardaway JC, Dhakal M, Wan X, Hoeman CM, Zaghouani S, Rowland LM, Tartar DM, VanMorlan AM, and Zaghouani H
- Subjects
- Animals, Antigen-Presenting Cells chemistry, Antigen-Presenting Cells drug effects, Antigen-Presenting Cells immunology, Bone Marrow Cells chemistry, Cell Lineage, Cell Movement, Cells, Cultured, Female, Gene Knock-In Techniques, Granulocyte-Macrophage Progenitor Cells chemistry, Granulocyte-Macrophage Progenitor Cells drug effects, Granulocyte-Macrophage Progenitor Cells immunology, Interleukin-13 pharmacology, Interleukin-13 Receptor alpha1 Subunit deficiency, Interleukin-13 Receptor alpha1 Subunit genetics, Lymphocytes, Null cytology, Lymphopoiesis, Male, Mice, Mice, Congenic, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Sequence Deletion, T-Lymphocytes cytology, Antigen-Presenting Cells cytology, Antigens, Differentiation analysis, Bone Marrow Cells classification, Granulocyte-Macrophage Progenitor Cells cytology, Interleukin-13 Receptor alpha1 Subunit analysis, Myelopoiesis, Thymus Gland cytology
- Abstract
The earliest thymic progenitors (ETPs) were recently shown to give rise to both lymphoid and myeloid cells. Whereas the majority of ETPs are derived from IL-7Rα-positive cells and give rise exclusively to T cells, the origin of the myeloid cells remains undefined. In this study, we show both in vitro and in vivo that IL-13Rα1(+) ETPs yield myeloid cells with no potential for maturation into T cells, whereas IL-13Rα1(-) ETPs lack myeloid potential. Moreover, transfer of lineage-negative IL-13Rα1(+) bone marrow stem cells into IL-13Rα1-deficient mice reconstituted thymic IL-13Rα1(+) myeloid ETPs. Myeloid cells or macrophages in the thymus are regarded as phagocytic cells whose function is to clear apoptotic debris generated during T cell development. However, the myeloid cells derived from IL-13Rα1(+) ETPs were found to perform Ag-presenting functions. Thus, IL-13Rα1 defines a new class of myeloid restricted ETPs yielding APCs that could contribute to development of T cells and the control of immunity and autoimmunity.
- Published
- 2012
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