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Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells.
Nat Immunol. 2008 Aug; 9(8):917-26.NI

Abstract

The costimulatory molecule 4-1BB and its ligand 4-1BBL can control adaptive immunity, but here we show that their interaction also suppressed myelopoiesis. We found that 4-1BBL was expressed on hematopoietic stem cells, differentiating common myeloid progenitors and granulocyte-macrophage progenitors, and 4-1BB was inducible on activated myeloid progenitors. Steady-state numbers of granulocyte-macrophage progenitors, myeloid-lineage cells and mature dendritic cells were higher in 4-1BB- and 4-1BBL-deficient mice, indicative of a negative function, and we confirmed that result with bone marrow chimeras and in vitro, where the absence of interactions between 4-1BB and 4-1BBL led to enhanced differentiation into dendritic cell lineages. The regulatory activity was mediated by 4-1BBL, with binding by 4-1BB inhibiting differentiation of myeloid progenitors. Thus, 4-1BB and 4-1BBL have a previously unknown function in limiting myelopoiesis and the development of dendritic cells.

Authors+Show Affiliations

Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18604213

Citation

Lee, Seung-Woo, et al. "Identification of Regulatory Functions for 4-1BB and 4-1BBL in Myelopoiesis and the Development of Dendritic Cells." Nature Immunology, vol. 9, no. 8, 2008, pp. 917-26.
Lee SW, Park Y, So T, et al. Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells. Nat Immunol. 2008;9(8):917-26.
Lee, S. W., Park, Y., So, T., Kwon, B. S., Cheroutre, H., Mittler, R. S., & Croft, M. (2008). Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells. Nature Immunology, 9(8), 917-26. https://doi.org/10.1038/ni.1632
Lee SW, et al. Identification of Regulatory Functions for 4-1BB and 4-1BBL in Myelopoiesis and the Development of Dendritic Cells. Nat Immunol. 2008;9(8):917-26. PubMed PMID: 18604213.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells. AU - Lee,Seung-Woo, AU - Park,Yunji, AU - So,Takanori, AU - Kwon,Byoung S, AU - Cheroutre,Hilde, AU - Mittler,Robert S, AU - Croft,Michael, Y1 - 2008/07/06/ PY - 2008/05/02/received PY - 2008/06/11/accepted PY - 2008/7/8/pubmed PY - 2008/10/10/medline PY - 2008/7/8/entrez SP - 917 EP - 26 JF - Nature immunology JO - Nat Immunol VL - 9 IS - 8 N2 - The costimulatory molecule 4-1BB and its ligand 4-1BBL can control adaptive immunity, but here we show that their interaction also suppressed myelopoiesis. We found that 4-1BBL was expressed on hematopoietic stem cells, differentiating common myeloid progenitors and granulocyte-macrophage progenitors, and 4-1BB was inducible on activated myeloid progenitors. Steady-state numbers of granulocyte-macrophage progenitors, myeloid-lineage cells and mature dendritic cells were higher in 4-1BB- and 4-1BBL-deficient mice, indicative of a negative function, and we confirmed that result with bone marrow chimeras and in vitro, where the absence of interactions between 4-1BB and 4-1BBL led to enhanced differentiation into dendritic cell lineages. The regulatory activity was mediated by 4-1BBL, with binding by 4-1BB inhibiting differentiation of myeloid progenitors. Thus, 4-1BB and 4-1BBL have a previously unknown function in limiting myelopoiesis and the development of dendritic cells. SN - 1529-2916 UR - https://www.unboundmedicine.com/medline/citation/18604213/Identification_of_regulatory_functions_for_4_1BB_and_4_1BBL_in_myelopoiesis_and_the_development_of_dendritic_cells_ L2 - https://doi.org/10.1038/ni.1632 DB - PRIME DP - Unbound Medicine ER -