The Effect Of Chemokine-like Factor 1 (CKLF1) On Imiquimod Induced Mice Psoriasis-like Model

Psoriasis is an epidermal proliferation and inflammation of the autoimmune skin disease,the skin lesions are characterized by keratinocyte proliferation and differentiation accelerated intradermal capillary proliferation and expansion,accompanied by a large number of T cells continued infiltration.Imidocormone-induced mouse psoriasis model is a more successful and easy-to-use model.The model of skin lesions,histopathological features and related cytokine changes are similar to psoriasis.Chemokine-Like Factor 1(CKLF1)is a chemokine with CC chemokine and chemotaxis.It participates in a variety of autoimmune diseases and allergic pathologies.Broad-spectrum chemotactic activity and cell proliferation,and its important functional receptors are CCR4 and CCR5.CCR4 is mainly expressed in dendritic cells,T lymphocytes,especially Th17 cells,Treg cells and other surfaces,in mediating the homing of T cells play an important role.The C-terminal derived peptides C19 and C27 of CKLF1 all act on the CCR4 receptor.C19 has a weak chemokine receptor activation and a strong receptor-deprivation ability,which is a chemokine receptor antagonist.Objective In this study,we will the observe effects of CKLF1-C19 and CKLF1-C27 onimidacretine-induced psoriasis-like lesions in mice and the regulation of inflammatory cell infiltration and IL-23 and IL-17 A m RNA expressio.Reveal the role of CKLF1 in the pathogenesis of psoriasis.Materials and methods Male Balb/c mice were randomly divided into blank control group,model group,C19 group and C27 group.The mices were separately given vaseline cream,imiquimod cream,imiquimod cream and C19,imiquimod cream and C27 were treated once for 6 consecutive days.The skin of the back of the mice was digitally imaged and the PASI score was recorded.On the 6th day,the mice were sacrificed by spinal dislocation.The expression of CD3,CD31,Ki-67 and MPO in the skin lesions of mice were detected by immunohistochemical method.The expression of IL-23 in the lesions was detected by real-time fluorescence quantitative PCR.IL-17 m RNA expression.The results 1.Continuous apply IMQ in the back of the mouse skin,can be successfully induced mouse psoriasis-like lesions.In 2-3 days IMQ group back skin appears small scales,skin folds,in 6 days skin tuns dark red,scales are layered,the skin thickening significantly.IMQ group HE staining shows that the epidermal highly hyperplasia,accompanied by the emergence of Munro micro abscess,dermal inflammatory cells infiltration significantly,vascular proliferation and expansion.2.C19 group IMQ-induced psoriasis-like lesions reduced,the performance of skin erythema color than IMQ group shallow,scaly reduction,reduce the degree of skin infiltration.The degree of inhibition was dose-dependent(10μg group = 20μg group> 5μg group> 0.5μg group),PASI score was different(P <0.05).The expression of Ki-67,CD3,CD31 and MPO in the lesion was lower than that in the IMQ group.3.Local intradermal injection of C27 can promote the production of psoriasis-likelesions,showing an increase in the degree of skin infiltration.The expression of Ki-67,CD3,CD31 and MPO in skin lesions was higher than that in IMQ group.1 4.Compared with the blank group,IL-23 and IL-17 m RNA expression in IMQ group increased.Compared with IMQ group,the expression of IL-23 and IL-17 m RNA in C19 group was lower than that in IMQ group,and the difference was statistically significant(P <0.05).Conclusion 1.Imidocormone-induced mouse psoriasis-like model was established successfully.2.In the psoriasis model,C27 can promote the infiltration of T cells and neutrophils in the lesion,promote the proliferation of vascular endothelial cells and the proliferation of keratinocytes,and increase the expression of local IL-23 and IL-17 A m RNA.3.In the psoriasis model,C19 can reduce the infiltration of T cells and neutrophils in the lesion,inhibit the proliferation of vascular endothelial cells and the proliferation of keratinocytes,and decrease the expression of local IL-23 and IL-17 A m RNA.4.C19 can inhibit the promotion of C27 in psoriasis mouse model.