Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain

Author:

Anandasabapathy Niroshana11,Victora Gabriel D.122,Meredith Matthew1,Feder Rachel11,Dong Baojun3,Kluger Courtney11,Yao Kaihui1,Dustin Michael L.22,Nussenzweig Michel C.11,Steinman Ralph M.11,Liu Kang13

Affiliation:

1. Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Laboratory of Molecular Immunology, and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065

2. Helen L. and Martin S. Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine and Department of Pathology, New York University School of Medicine, New York, NY 10016

3. Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032

Abstract

Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences in expression of transcripts encoding surface molecules, transcription factors, pattern recognition receptors, and other genes in m/chDCs compared with monocytes and microglia. Migrating pre-DC progenitors from bone marrow gave rise to m/chDCs that had a 5–7-d half-life. In contrast to microglia, DCs actively present self-antigens and stimulate T cells. Therefore, the meninges and choroid plexus of a steady-state brain contain DCs that derive from local precursors and exhibit a differentiation and antigen-presenting program similar to spleen DCs and distinct from microglia.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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