The Observation Of TSLP/OX40L/IL-13 Pathway In Severe Alopecia Areata And Topical Immunotherapy With DPCP

Objective: Alopecia areata(AA)is a common autoimmune inflammatory alopecia.At present,the pathogenesis of AA is not yet clear,and the study on Th2 immune status and its role in the pathogenesis of severe AA is rare.The mechanism of local immunotherapy with DPCP for treatment of severe AA is still being explored,and there is less research on Th2-related factors after local immunotherapy with DPCP.The TSLP/OX40L/IL-13 pathway has always been considered as an important signaling pathway to initiate and maintain a Th2-type immune response.There is no report on TSLP/OX40L/IL-13 pathway in severe AA and local immunotherapy with DPCP.The purpose of this study is to investigate the role of TSLP/OX40L/IL-13 pathway in the pathogenesis of severe AA,and to observe the changes of this pathway in patients with severe AA before and after local immunotherapy with DPCP,and to initially investigate the role of TSLP/OX40L/IL-13 pathway in local immunotherapy with DPCP.Methods: 1.We enrolled 33 patients with severe AA and 20 healthy people.Enzyme immunosorbent assay(ELISA)was used to detect the expression levels of TSLP,Th2 cytokines such as IL-4,interleukin-5(IL-5)and IL-13,and Th1 cytokines Interferon-?(IFN-?)in peripheral blood serum.Thirty-three cases of scalp lesions in patients with severe AA and 20 cases of normal scalp tissue were collected as observation specimens and the expression levels of TSLP,OX40 L,Th2-type cytokines(IL-4,IL-5,IL-13)and Th1-type cytokines(IFN-?)in scalp specimens were detected by Reverse Transcription and Polymerase Chain Reaction(RT-PCR).2.The above 33 patients with severe AA were treated with local immunotherapy with DPCP.After DPCP treatment,21 patients were in the respond group and 12 patients were in the non-respond group.The serum levels of TSLP,Th2 type cytokines(IL-4,IL-5,IL-13)and Th1 type cytokines(IFN-?)were detected by ELISA.3.All the experimental data were sorted out and statistically analyzed by SPSS 19.0 software,and all the statistical results were analyzed by two-sided test.P<0.05 was considered to have statistical significance.Results: 1.The levels of TSLP and IL-5 were significantly lower than that in the normal control group(P<0.01),the expression level of IFN-? was significantly higher than that in the normal control group(P<0.01).The expression levels of TSLP,OX40 L,IL-4 and IL-13 mRNA in scalp of severe AA were significantly lower than those in the normal control group(P<0.01),and the expression level of IFN-? mRNA was significantly higher than that in the normal control group(P<0.01).2.After local immunotherapy with DPCP,the serum expression levels of TSLP,IL-5 and IL-13 in peripheral blood of 33 patients with severe AA were significantly higher than those before treatment(P<0.01).The expression levels of TSLP and IL-13 were higher than normal levels,and the expression level of IL-5 increased to normal level.The expression level of IFN-? was significantly lower than before treatment(P<0.01),and decreased to normal level.Before local immunotherapy with DPCP,the serum expression levels of TSLP and IL-5 in the respond group were lower than normal levels(P<0.01,0.05).The expression level of IFN-? was significantly higher than normal level(P<0.01).The expression of cytokines in the respond group after local immunotherapy with DPCP showed a similar overall trend.After local immunotherapy with DPCP,the expression levels of TSLP,IL-5 and IL-13 were significantly increased than pre-treatment(P<0.01),and were higher than normal levels.The expression level of IFN-? was significantly lower than pre-treatment(P<0.01)and decreased to normal level.The serum expression levels of TSLP,IL-4,IL-13 and IFN-? in the non-respond group had no significant difference before and after local immunotherapy with DPCP(P>0.05),TSLP and IL-13 were at normal levels,while IL-4 and IFN-? were higher than normal levels.The serum expression of TSLP,IL-4 and IL-13 in the respond group before local immunotherapy with DPCP was lower than that in the non-respond group(P<0.01).The serum expression levels of TSLP and IL-13 in the respond group after local immunotherapy with DPCP were significantly higher than that in the non-respond group(P<0.01),while the expression level of IFN-? was significantly lower than that in the non-respong group(P<0.01).3.The expression levels of TSLP,OX40 L and IL-13 mRNA in the local scalp lesions of the respond group before topical immunotherapy with DPCP were significantly lower than normal levels(P<0.01),the expression level of IFN-? mRNA was significantly higher than normal level(P<0.01).Before topical immunotherapy with DPCP,the expression levels of TSLP,OX40 L,and IL-13 mRNA in the scalp lesions of the non-respond group had no significant difference from the normal levels(P>0.05),but significantly higher than that of the respond group(P<0.01),the expression level of IFN-? mRNA was significantly higher than normal level(P<0.01).Conclusion:1.There exists downregulation of TSLP/OX40L/IL-13 pathway in the patients with severe AA and Th1/Th2 immune imbalance.2.After local immunotherapy with DPCP,the TSLP/OX40L/IL-13 pathway is significantly up-regulated in the respond group.As a contact sensitizer,DPCP may play a therapeutic role by up-regulating the Th2 immune and reconstruct Th1/Th2 balance in patients with severe AA.