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PMID: 16444257 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langerhans cells arise from monocytes in vivo.

Nature immunology ·Vol. 7 ·No. 3 ·2006-03-00 ·Pages 265-73

Ginhoux F, Tacke F, Angeli V, Bogunovic M, Loubeau M, Dai XM, Stanley ER, Randolph GJ, Merad M

Abstract

Langerhans cells (LCs) are the only dendritic cells of the epidermis and constitute the first immunological barrier against pathogens and environmental insults. The factors regulating LC homeostasis remain elusive and the direct circulating LC precursor has not yet been identified in vivo. Here we report an absence of LCs in mice deficient in the receptor for colony-stimulating factor 1 (CSF-1) in steady-state conditions. Using bone marrow chimeric mice, we have established that CSF-1 receptor-deficient hematopoietic precursors failed to reconstitute the LC pool in inflamed skin. Furthermore, monocytes with high expression of the monocyte marker Gr-1 (also called Ly-6c/G) were specifically recruited to the inflamed skin, proliferated locally and differentiated into LCs. These results identify Gr-1(hi) monocytes as the direct precursors for LCs in vivo and establish the importance of the CSF-1 receptor in this process.

MeSH Terms
Animals Cell Differentiation Cell Lineage/immunology Female Flow Cytometry Hematopoietic Stem Cells Immunohistochemistry Langerhans Cells/cytology,immunology Macrophage Colony-Stimulating Factor/deficiency,immunology Mice Mice, Congenic Monocytes/cytology,immunology Receptors, Chemokine/immunology,metabolism
Chemicals
Gr-1 protein, mouse Receptors, Chemokine Macrophage Colony-Stimulating Factor
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ginhoux Florent
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Tacke Frank
Angeli Veronique
Bogunovic Milena
Loubeau Martine
Dai Xu-Ming
Stanley E Richard
Randolph Gwendalyn J
Merad Miriam
References (53)
53 references, click to expand
  1. Ontogeny of Langerin/CD207 expression in the epidermis of mice.
    J Invest Dermatol. 2004 Mar;122(3):670-2 PMID: 15086552
  2. Distribution of cells bearing receptors for a colony-stimulating factor (CSF-1) in murine tissues.
    J Cell Biol. 1981 Dec;91(3 Pt 1):848-53 PMID: 6276411
  3. Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs.
    Nature. 1994 Apr 14;368(6472):643-8 PMID: 8145851
  4. Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine.
    Cancer Res. 2001 Sep 1;61(17):6451-8 PMID: 11522640
  5. Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1(op)/Csf1(op)) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis.
    Blood. 2001 Jul 1;98(1):74-84 PMID: 11418465
  6. Hematological characterization of congenital osteopetrosis in op/op mouse. Possible mechanism for abnormal macrophage differentiation.
    J Exp Med. 1982 Nov 1;156(5):1516-27 PMID: 7130905
  7. Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications.
    J Immunol Methods. 1994 Sep 14;174(1-2):83-93 PMID: 8083541
  8. Differentiation of epidermal Langerhans cells in macrophage colony-stimulating-factor-deficient mice homozygous for the osteopetrosis (op) mutation.
    J Invest Dermatol. 1992 Nov;99(5):46S-47S PMID: 1431208
  9. The Nikolas Symposia and histiocytosis.
    Nat Rev Cancer. 2005 Jun;5(6):488-94 PMID: 15928676
  10. Flk2+ myeloid progenitors are the main source of Langerhans cells.
    Blood. 2006 Feb 15;107(4):1383-90 PMID: 16263793
  11. Is the osteopetrotic (op/op mutant) mouse completely deficient in expression of macrophage colony-stimulating factor?
    J Interferon Cytokine Res. 1995 Apr;15(4):279-84 PMID: 7627801
  12. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells.
    Immunity. 2005 May;22(5):643-54 PMID: 15894281
  13. CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue.
    Immunity. 2000 May;12(5):495-503 PMID: 10843382
  14. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha.
    J Exp Med. 1996 Aug 1;184(2):695-706 PMID: 8760823
  15. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy.
    Cell. 1982 Jan;28(1):71-81 PMID: 6978185
  16. Cytokine regulation of the macrophage (M phi) system studied using the colony stimulating factor-1-deficient op/op mouse.
    Physiol Rev. 1996 Oct;76(4):927-47 PMID: 8874489
  17. Increased blood myeloid dendritic cells and dendritic cell-poietins in Langerhans cell histiocytosis.
    J Immunol. 2005 Mar 1;174(5):3067-71 PMID: 15728521
  18. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response.
    J Immunol. 2004 Apr 1;172(7):4410-7 PMID: 15034056
  19. Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse.
    J Cell Sci. 1993 Apr;104 ( Pt 4):1021-9 PMID: 8314887
  20. Ontogeny of Ia-positive and Thy-1-positive leukocytes of murine epidermis.
    J Invest Dermatol. 1986 Feb;86(2):129-33 PMID: 2875114
  21. The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting.
    J Exp Med. 2002 Aug 19;196(4):517-27 PMID: 12186843
  22. The biology of CSF-1 and its receptor.
    Curr Top Microbiol Immunol. 1992;181:141-67 PMID: 1424779
  23. Dermal-resident CD14+ cells differentiate into Langerhans cells.
    Nat Immunol. 2001 Dec;2(12):1151-8 PMID: 11702065
  24. Cutaneous CXCL14 targets blood precursors to epidermal niches for Langerhans cell differentiation.
    Immunity. 2005 Sep;23(3):331-42 PMID: 16169505
  25. Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice.
    J Clin Invest. 1997 Nov 15;100(10):2552-61 PMID: 9366570
  26. Epidermal viral immunity induced by CD8alpha+ dendritic cells but not by Langerhans cells.
    Science. 2003 Sep 26;301(5641):1925-8 PMID: 14512632
  27. Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-beta1-dependent cells.
    Int Immunol. 2001 May;13(5):695-704 PMID: 11312257
  28. Transforming growth factor beta1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells.
    J Exp Med. 1998 Mar 16;187(6):961-6 PMID: 9500798
  29. Mouse pre-immunocytes as non-proliferating multipotent precursors of macrophages, interferon-producing cells, CD8alpha(+) and CD8alpha(-) dendritic cells.
    Eur J Immunol. 2001 Nov;31(11):3403-12 PMID: 11745359
  30. Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity.
    J Cell Biol. 2005 May 23;169(4):569-76 PMID: 15897263
  31. Enforced expression of Bcl-2 in monocytes rescues macrophages and partially reverses osteopetrosis in op/op mice.
    Cell. 1997 Jun 27;89(7):1021-31 PMID: 9215625
  32. A stochastic model of self-renewal and commitment to differentiation of the primitive hemopoietic stem cells in culture.
    J Cell Physiol. 1982 Dec;113(3):455-8 PMID: 7174743
  33. A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: the skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells.
    J Exp Med. 1996 Dec 1;184(6):2417-22 PMID: 8976197
  34. Identification and characterization of a novel monocyte subpopulation in human peripheral blood.
    Blood. 1989 Nov 15;74(7):2527-34 PMID: 2478233
  35. Characterization of a common precursor population for dendritic cells.
    Nature. 2002 Feb 28;415(6875):1043-7 PMID: 11875574
  36. Langerhans cells renew in the skin throughout life under steady-state conditions.
    Nat Immunol. 2002 Dec;3(12):1135-41 PMID: 12415265
  37. Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease.
    Nat Med. 2004 May;10(5):510-7 PMID: 15098028
  38. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro.
    J Exp Med. 1985 Mar 1;161(3):526-46 PMID: 3871837
  39. Blood monocytes consist of two principal subsets with distinct migratory properties.
    Immunity. 2003 Jul;19(1):71-82 PMID: 12871640
  40. A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells.
    J Immunol. 1999 Aug 1;163(3):1409-19 PMID: 10415041
  41. Immature monocytes acquire antigens from other cells in the bone marrow and present them to T cells after maturing in the periphery.
    J Exp Med. 2006 Mar 20;203(3):583-97 PMID: 16492803
  42. Osteoclast deficiency results in disorganized matrix, reduced mineralization, and abnormal osteoblast behavior in developing bone.
    J Bone Miner Res. 2004 Sep;19(9):1441-51 PMID: 15312244
  43. Chemokine Up-regulation and activated T cell attraction by maturing dendritic cells.
    Science. 1999 Apr 30;284(5415):819-22 PMID: 10221917
  44. Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse.
    Development. 1994 Jun;120(6):1357-72 PMID: 8050349
  45. CSF-1 regulation of the wandering macrophage: complexity in action.
    Trends Cell Biol. 2004 Nov;14(11):628-38 PMID: 15519852
  46. The granulocyte-macrophage colony-stimulating factors.
    Science. 1985 Jul 5;229(4708):16-22 PMID: 2990035
  47. Investigations of a stochastic model of haemopoiesis.
    Exp Hematol. 1973;1(6):362-75 PMID: 4803030
  48. Langerhans cells activate naive self-antigen-specific CD8 T cells in the steady state.
    Immunity. 2004 Sep;21(3):391-400 PMID: 15357950
  49. Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitization.
    J Immunol. 1990 Nov 1;145(9):2833-8 PMID: 2212665
  50. The effect of human recombinant macrophage colony-stimulating factor (CSF-1) on the murine mononuclear phagocyte system in vivo.
    J Immunol. 1988 Nov 15;141(10):3405-9 PMID: 3053899
  51. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects.
    Blood. 2002 Jan 1;99(1):111-20 PMID: 11756160
  52. Maturational steps of bone marrow-derived dendritic murine epidermal cells. Phenotypic and functional studies on Langerhans cells and Thy-1+ dendritic epidermal cells in the perinatal period.
    J Immunol. 1989 Oct 15;143(8):2431-8 PMID: 2571637
  53. Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes.
    J Exp Med. 2004 Nov 15;200(10):1231-41 PMID: 15534368
Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2908
DOI
10.1038/ni1307
Published
2006-03-00
Epub
2006-00-29
Pages
265-73
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC4727824
Subset
IM
Grants
NCI NIH HHS · R01 CA032551 · United States
NCI NIH HHS · R37 CA026504 · United States
NIAID NIH HHS · R01 AI049653 · United States
NIAID NIH HHS · AI49653 · United States
NCI NIH HHS · CA32551 · United States
NCI NIH HHS · CA26504 · United States
NCI NIH HHS · R01 CA026504 · United States
Corrections
CommentIn
PMID: 16482165
External Links
PubMed source DOI: 10.1038/ni1307 PMC Full Text View journal details
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