title: CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells.
abstract: CXCL17 is expressed in a variety of cancers and promotes tumor progression by recruiting myeloid-derived suppressor cells (MDSCs). MDSCs suppress tumor immunity by attracting regulatory T cells (Tregs) into tumor sites through CCL5. In this study, we examined the role of CXCL17 in skin disorders. CXCL17 mRNA levels in psoriasis skin, but not in lesional skin of atopic dermatitis or cutaneous T cell lymphoma, were significantly higher than those in normal skin. CXCL17 was mainly expressed in the epidermis, and IFN-γ dose-dependently increased CXCL17 expression by human keratinocytes in vitro. As CXCL17 mRNA expression was increased by treatment with imiquimod (IMQ), we examined the effects of CXCL17 in IMQ-induced psoriasis-like skin inflammation. Injection of recombinant CXCL17 into the ear before and during IMQ application decreased ear thickness, inflammatory cytokine expression, and the number of infiltrating cells compared with PBS injection. Flow cytometric analysis and immunofluorescent staining revealed that the numbers of MDSCs, which are CD11b+Gr-1+, and that of Tregs, which are CD4+CD25+, were higher in the ear of the CXCL17-injected mice than in PBS-injected mice. MDSCs, but not Tregs, showed chemotaxis to CXCL17 in vitro. When mice were injected with anti-CCL5 Ab or anti-CCL4 Ab simultaneously with recombinant CXCL17, ear thickness and cytokine expression increased to a similar level of mice treated with PBS and control IgG, suggesting that these chemokines were important for anti-inflammatory effects. Taken together, CXCL17 attenuates IMQ-induced psoriasis-like skin inflammation by recruiting MDSCs and Tregs, which may be important for regulating excessive inflammation in psoriasis skin.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Tomonori
authors.identifier: 0000-0001-7362-3207
authors.initials: T
authors.lastname: Oka
authors.affiliation: Department of Dermatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan sugayam-der@h.u-tokyo.ac.jp.
authors.forename: Makoto
authors.identifier: 0000-0002-1618-329X
authors.initials: M
authors.lastname: Sugaya
authors.affiliation: Department of Dermatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Dermatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyagaki
authors.affiliation: Department of Dermatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Yoshihide
authors.identifier: 0000-0001-5560-9778
authors.initials: Y
authors.lastname: Asano
authors.affiliation: Department of Dermatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Shinichi
authors.identifier: 0000-0001-5519-172X
authors.initials: S
authors.lastname: Sato
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D054407:Chemokine CCL4 / Q000276:immunology; D018946:Chemokine CCL5 / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology*; D019743:Chemokines, CXC / Q000276:immunology*; D002633:Chemotaxis; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003872:Dermatitis / Q000188:drug therapy / Q000276:immunology; D004817:Epidermis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D000077271:Imiquimod; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology; D012867:Skin / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: D000634:Aminoquinolines; C508524:CXCL17 protein, human; C000591605:CXCL17 protein, mouse; C503460:Ccl5 protein, mouse; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D000077271:Imiquimod