title: Intestinal CX3C chemokine receptor 1(high) (CX3CR1(high)) myeloid cells prevent T-cell-dependent colitis.
abstract: Adequate activation of CD4(+) T lymphocytes is essential for host defense against invading pathogens; however, exaggerated activity of effector CD4(+) T cells induces tissue damage, leading to inflammatory disorders such as inflammatory bowel diseases. Several unique subsets of intestinal innate immune cells have been identified. However, the direct involvement of innate immune cell subsets in the suppression of T-cell-dependent intestinal inflammation is poorly understood. Here, we report that intestinal CX(3)C chemokine receptor 1(high) (CX(3)CR1(high)) CD11b(+) CD11c(+) cells are responsible for prevention of intestinal inflammation through inhibition of T-cell responses. These cells inhibit CD4(+) T-cell proliferation in a cell contact-dependent manner and prevent T-cell-dependent colitis. The suppressive activity is abrogated in the absence of the IL-10/Stat3 pathway. These cells inhibit T-cell proliferation by two steps. Initially, CX(3)CR1(high) CD11b(+) CD11c(+) cells preferentially interact with T cells through highly expressed intercellular adhesion molecule-1/vascular cell adhesion molecule-1; then, they fail to activate T cells because of defective expression of CD80/CD86. The IL-10/Stat3 pathway mediates the reduction of CD80/CD86 expression. Transfer of wild-type CX(3)CR1(high) CD11b(+) CD11c(+) cells prevents development of colitis in myeloid-specific Stat3-deficient mice. Thus, these cells are regulatory myeloid cells that are responsible for maintaining intestinal homeostasis.
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine,  Osaka University, Suita, Osaka, 565-0871,  Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Kayama
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Ueda
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Sawa
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Jeon
authors.forename: Ji Su
authors.initials: JS
authors.lastname: Ma
authors.forename: Ryu
authors.initials: R
authors.lastname: Okumura
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kubo
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.forename: Taku
authors.initials: T
authors.lastname: Okazaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D049109:Cell Proliferation; D003092:Colitis / Q000150:complications / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D016753:Interleukin-10 / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology*; D019707:Receptors, Chemokine / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000172:deficiency / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018845:CD11 Antigens; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016753:Interleukin-10