+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      FMS-like tyrosine kinase 3 is required for dendritic cell development in peripheral lymphoid tissues


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Dendritic cell (DC) development begins in the bone marrow but is not completed until after immature progenitors reach their sites of residence in lymphoid organs. The hematopoietic growth factors regulating these processes are poorly understood. Here we examine the effects of FMS-like tyrosine kinase 3 (Flt3) signaling on macrophage DC progenitors (MDP) in the bone marrow and on peripheral DCs. We find that the MDP compartment is responsive to super–physiologic levels of Flt3 ligand (Flt3L) but is not dependent on Flt3 for its homeostatic maintenance in vivo. In contrast, Flt3 is essential in regulation of homeostatic DC development in the spleen where it is required to maintain normal numbers of DCs by controlling their division in the periphery.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          Taking dendritic cells into medicine.

          Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.
            • Record: found
            • Abstract: found
            • Article: not found

            Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells.

            The ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3 (flt3), also referred to as fetal liver kinase-2 (flk-2), has an important role in hematopoiesis. The flt3 ligand (flt3L) is a growth factor for hematopoietic progenitors and induces hematopoietic progenitor and stem cell mobilization in vivo. In addition, when mice are treated with flt3L immature B cells, natural killer (NK) cells and dendritic cells (DC) are expanded in vivo. To further elucidate the role of flt3L in hematopoiesis, mice lacking flt3L (flt3L-/-) were generated by targeted gene disruption. Leukocyte cellularity was reduced in the bone marrow, peripheral blood, lymph nodes (LN), and spleen. Thymic cellularity, blood hematocrit, and platelet numbers were not affected. Significantly reduced numbers of myeloid and B-lymphoid progenitors were noted in the BM of flt3L-/- mice. In addition a marked deficiency of NK cells in the spleen was noted. DC numbers were also reduced in the spleen, LN, and thymus. Both myeloid-related (CD11c(++) CD8alpha(-)) and lymphoid-related (CD11c(++) CD8alpha(+)) DC numbers were affected. We conclude that flt3L has an important role in the expansion of early hematopoietic progenitors and in the generation of mature peripheral leukocytes.
              • Record: found
              • Abstract: found
              • Article: not found

              Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo.

              Dendritic cells (DCs) comprise several subsets, and their roles in the presentation of antigens derived from pathogens, vaccines and self tissues are now beginning to be elucidated. Differences in location, life cycle and intrinsic abilities to capture, process and present antigens on their MHC class I and class II molecules enable each DC subset to have distinct roles in immunity to infection and in the maintenance of self tolerance. Unexpected interactions among DC subsets have also been revealed. These interactions, which allow the integration of the intrinsic abilities of different DC types, enhance the ability of the DC network to respond to multiple scenarios of infection.

                Author and article information

                Nat Immunol
                Nat. Immunol.
                Nature immunology
                20 August 2009
                11 May 2008
                June 2008
                17 September 2009
                : 9
                : 6
                : 676-683
                [1 ]Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, 10065–6399
                [2 ]Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029
                [3 ]Howard Hughes Medical Institute, The Rockefeller University, New York, New York, 10065–6399
                Author notes
                Correspondence should be addressed to: C.W. ( claudia.waskow@ 123456crt-dresden.de ), Phone: +49-351-458-6520, Fax: +49-351-458-6309
                Funded by: National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
                Award ID: P01 AI051573-060004 || AI
                Funded by: Howard Hughes Medical Institute :
                Award ID: || HHMI_



                Comment on this article