CCR6 regulates the function of alloreactive and regulatory CD4+ T cells during acute graft-versus-host disease.
The chemokine receptor CCR6 is expressed by CD4+ T cell effector/memory and regulatory effector/memory (TREM) subsets. Here we show that CCR6 modulates graft-versus-host-disease (GVHD) responses in both alloreactive CD4+ T effector cells and regulatory T (Treg) cells. Mortality and morbidity due to acute GVHD were drastically reduced and delayed when naïve T cells were derived from CCR6-deficient donor mice. This deficiency also affected the suppressive ability of Treg cells in GVHD. CCR6-/- Treg cells were able to suppress T cell proliferation in vitro, but their in vivo capacity to downregulate target tissue damage induced by naïve wild type (WT) T cells was impaired. The data demonstrate a requirement for CCR6 in CD4+ T cell function in GVHD, in both effector and regulatory cell subsets.
Varona
Rosa
R
Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Darwin 3, Universidad Autónoma de Madrid, Cantoblanco, E-28049, Madrid, Spain.
Cadenas
Vanesa
V
Lozano
María
M
Moreno-Ortiz
Maria Carmen
MC
Kremer
Leonor
L
Martínez-A
Carlos
C
Márquez
Gabriel
G
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D007109:Immunity; D051379:Mice; D018345:Mice, Knockout; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C498126:CCR6 protein, mouse; D054399:Receptors, CCR6; D019707:Receptors, Chemokine