Role of CCL17 in the generation of cutaneous inflammatory reactions in Hu-PBMC-SCID mice grafted with human skin.
CCL17 may be of interest in skin inflammation, because it mainly attracts T cells expressing the cutaneous homing receptor and binds the chemokine receptor CCR4, preferentially expressed on Th-2 cells. We evaluated the in vivo effect of CCL17 injection in a humanized mouse model. (125)I-CCL17 injection into human skin grafted on severe combined immunodeficient (SCID) mice reconstituted with peripheral blood mononuclear cells resulted in a rapid transportation of CCL17 from the skin to the homolateral lymph nodes, followed 3 hours later by a lymph node infiltration of human memory CD4+ cells and dendritic cells. Intradermal injection of CCL17 resulted 24 hours later in a cutaneous recruitment of human memory CD4+ cells, monocytes, and basophils, but also murine eosinophils. In SCID mice reconstituted with polarized Th-1 or Th-2 cells, intradermal injection of CCL17 resulted in the recruitment of IL-4+ Th-2 cells but not of IFN-gamma+ Th-1 cells, whereas CCL17 was able to recruit both subsets in vitro. These results suggest that, in a humanized in vivo model, CCL17 is sufficient per se to induce a lymph node recruitment of memory CD4+ and dendritic cells and a cutaneous recruitment of Th-2-type cells, stressing it as an important actor in the initiation and development of Th-2-associated skin inflammation.
Gilet
Jules
J
U774 INSERM, Institut Pasteur de Lille, Lille cedex, France.
Chang
Ying
Y
Chenivesse
Cécile
C
Legendre
Benjamin
B
Vorng
Han
H
Duez
Catherine
C
Wallaert
Benoît
B
Porte
Henri
H
Senechal
Stéphanie
S
Tsicopoulos
Anne
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002465:Cell Movement; D054414:Chemokine CCL17 / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000209:etiology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D054398:Receptors, CCR4 / Q000032:analysis; D012867:Skin / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology*; D018418:Th2 Cells / Q000502:physiology; D014183:Transplantation, Heterologous / Q000276:immunology*
C106230:CCL17 protein, human; C499538:Ccl17 protein, mouse; C515355:Ccr4 protein, mouse; D054414:Chemokine CCL17; D016207:Cytokines; D054398:Receptors, CCR4