The Role Of Skin Derived IL-33/ST2 Inskin Transplantation And Psoriasis

Background: IL-33 is a new member of the cytokine IL-1 family,constitutively expressed in the skin of humans and mice,and its known recognized receptor is ST2.IL-33 is localized in the nucleus under physiological conditions.When the cells are necrotic and lysed,IL-33 in the nucleus is passively released to the outside of the cell,exerting the function of cytokines and regulating the immune response.The role of IL-33/ST2 in transplantation immunity is still unclear.IL-33 can down-regulate Th1-type immune response and regulate Treg to suppress immune rejection in heart transplantation;IL-33 is a key molecule in kidney transplantation.Aggravation of ischemia-reperfusion injury exacerbates rejection.Psoriasis is an autoimmune dermatitis mediated by Th1 and Th17 immune responses.The IL-33/ST2 pathway plays an important role in the development of the disease,but where the role of IL-33 is still unclear.In this paper,in order to better illustrate the role of IL-33/ST2 signaling pathway in the skin.in the first part,the skin transplantation model of bm12 mice to C57BL/6(WT/ST2-/-)mice was constructed and transplanted.Rejection scores and pathology of transplanted skin were studied to investigate the role of IL-33/ST2 in skin graft rejection.In the second part,mice with local skin IL-33 deletion were constructed by skin transplantation to explore the effect of local skin IL-33 on psoriasis.Purpose:(1)Explore the role of the IL-33/ST2 signaling pathway in skin graft rejection.(2)Explore the role of localized IL-33 in psoriasis.Method:(1)PCR confirmed ST2 knockout mice and bm12 mice.(2)Establish a skin graft rejection model of mouse MHC-II molecular mismatch,and observe the degree of rejection by HE staining.(3)The dorsal skin of C57BL/6-Tg(CAG-EGFP)mice was transplanted into the back of C57BL/6 mice,and the immune cell regeneration time in the transplanted skin was detected by immunofluorescence.(4)Skin transplantation method The mouse with local IL-33 deletion was established.After three weeks,the skin of the mice was continuously applied with imiquimod for 5 days to make the transplanted skin have psoriasis-like dermatitis and observe serious diseases.degree.Result(1)Confirmed that ST2 knockout mice and bm12 mice are homozygous.(2)In the skin graft rejection of bm12—C57BL/6,when the recipient's ST2 knocked out,the skin rejection was weakened and the graft skin survival time was prolonged.(3)In the skin graft rejection of bm12—C57BL/6,when the transplant donor ST2 was knocked out,there was no effect on skin graft rejection.(4)In the skin graft rejection of bm12—C57BL/6,when the IL-33 of the recipient mouse was knocked out,the skin rejection was weakened and the graft skin survival time was prolonged.(5)IL-33/ST2 signaling pathway mainly affects the accumulation of eosinophils in transplanted skin in MHC-II rejection,thereby attenuating skin graft rejection.(6)After three weeks of skin transplantation,the immune cells originally settled in the transplanted skin were all renewed.(7)IMQ-induced psoriatic dermatitis worsened after skin local IL-33 knockout.Conclusions:(1)After transplant recipients with ST2 deletion or IL-33 deletion,MHC-II class mismatched skin graft rejection was alleviated,and graft survival time was prolonged.It has nothing to do with whether there is ST2 or IL-33 in the transplanted skin.(2)Psoriasis dermatitis is aggravated after partial IL-33 knockdown of the skin.