CCR6 regulates CD4+ T-cell-mediated acute graft-versus-host disease responses.
We studied the role of chemokine receptor CCR6 in acute graft-versus-host disease (GvHD), a pathology in which activated, host antigen-specific donor T cells selectively damage tissues such as skin, liver, and gut. GvHD incidence was reduced in major histocompatibility complex (MHC) class II-mismatched recipients of CD4+ T cells from CCR6-deficient donors. In MHC-matched/minor histocompatibility antigen-mismatched recipients of CD4+CD45RB(high) T cells from CCR6-deficient donors, infiltration of CD45+ and CD4+ cells to skin and gut, as well as lesion onset, were significantly delayed, and pathologic symptoms were milder. Consistent with this, in skin and gut of recipients of naive T cells from CCR6-deficient donors we observed lower levels of interferon gamma (IFN-gamma), interleukin 10 (IL-10), and the chemokines that control activated T-cell homing. We suggest a role for CCR6 in recruiting alloreactive CD4+ T cells to target tissues and identify CCR6 as a potential therapeutic target for GvHD.
Varona
Rosa
R
Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Cadenas
Vanesa
V
Gómez
Lucio
L
Martínez-A
Carlos
C
Márquez
Gabriel
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002455:Cell Division / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology*; D012720:Severity of Illness Index
C106311:CCR6 protein, human; D018925:Chemokines; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D054399:Receptors, CCR6; D019707:Receptors, Chemokine