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.

Notoginseng root enhances healing in imiquimod-induced psoriasis mice model via anti-inflammatory and antiproliferative properties

“…In the present study, treatment with PN gel significantly attenuated the altered expressions of inflammatory mediators in the skin tissue of imiquimod-induced psoriatic mice. This finding is consistent with previously published data [18].…”

Cxcl17 -/- mice develop exacerbated disease in a T cell-dependent autoimmune model

“…23 A recent report described that CXCL17 attenuates inflammation in a mouse psoriasis model through the recruitment of myeloid derived suppressor cells that can, in turn, recruit regulatory T cells (Tregs). 24 In the present study, we have continued the characterization of a Cxcl17 −/− mouse. We observed abnormalities in the numbers of several T cell populations in both spleen and LNs.…”

“…A recent report described that CXCL17 attenuates inflammation in a mouse psoriasis model through the recruitment of myeloid derived suppressor cells that can, in turn, recruit regulatory T cells (Tregs) …”

Aberrant expression of the UPF1 RNA surveillance gene disturbs keratinocyte homeostasis by stabilizing AREG

“…In addition, analysis for several other skin diseases was conducted by analyzing UPF1 expression profiles acquired from the GEO database. An independent sample test for Marfan syndrome (GDS2960) showed a significantly increased UPF1 expression in lesions compared with normal tissues, and multiple comparisons for squamous cell carcinoma (GDS2200) and melanoma (GDS1375) showed a high UPF1 expression in squamous cell carcinoma compared with actinic keratosis or normal tissues, and melanoma and benign nevi compared with normal tissues (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). A negative feedback regulatory network that directly acts on UPF1 in response to NMD perturbation has been identified in a previous study which demonstrated that UPF1 itself is a natural substrate of the NMD pathway (6).…”