The Researches About Functions Of IL-30 And Its Use On Treating Psoriasis

Psoriasis is a common form of organ specific autoimmune disease,even leads to some other related diseases,such as arthritis,etc.The pathogenesis of psoriasis is unclear.Both innate immunity and acquired immunity play key roles in its occurrence and development.Most of the studies believe that psoriasis is a kind of chronic inflammation mediated by T cells disease,T helper 1(Thl)and 17(Th 17)T helper cells,especially Th17 cells have a particularly important role in incidence and development in psoriasis.In addition,keratinocytes(keratinocytes,KCs)and dendritic cells(dendritic cells,DCs)also play important roles.In a word,psoriasis is a disease induced by the out of control cross-talk among KCs,DCs and T cells.IL-27p28,also known as IL-30,is a subunit of IL-27.IL-27p28 and Ebi3(Epstein-Barr virus-induced gene 3,Ebi3)could form heterologous dimers IL-27 through non-covalent bond.Recent studies showed that the secretion of IL-30 could independent of Ebi3 and played biological functions by itself.IL-30 is a natural antagonists of gp130,thus it could inhibite the differentiation of Th1 and Th17 from Naive CD4+ T cells.As IL-6 and IL-27 share gp 130 as a part of their receptors and mediate the polization of Th17 and Thl respectively.With the further studies,IL-30 might have its own signal pathway to participate in inhibiting the inflammatory response,and the activation of signaling pathways are gp 130 dependent.Due to the extensive existence of gp130,we concluded that IL-30 might have extensive functions.To sum up the above reasons,IL-30 might have therapeutic effects on treating psoriasis and other autoimmune diseases.In order to explore the potential effects of IL-30 on treating psoriasis and its treatment mechanism,we successfully realized the soluble expression of IL-30 and purified it using the method of affinity chromatography.Finally,we got recombination IL-30 with biological activities.In vitro,TNF-?,IL-17A,IL-22,IL-1? and OSM were used to treat HaCat cell line(human keratinization cell line)with or without IL-30 pretreatment.Results showed that the expression of psoriasis-related factors was reduced.Besides,IL-30 inhibited the expression of MHC?,CD40 and CD86 on the surface of DCs and reduced DCs mediated T lymphocyte proliferation.In vivo,K14-VEGF(vascular endothelial growth factor,VEGF)transgenic mice and imiquimod(IMQ)cream induced psoriasis-like models were used to simulate the psoriasis on paitent.Results showed that IL-30 can significantly inhibit the occurrence and development of sample psoriatic lesions.Psoriasis associated inflammatory factors and inflammatory cells were significantly reduced after treatment.In addition,we also use Ebi3-/-mice to creat psoriasis-like model using IMQ cream,surprisely,Ebi3-/-mice did not get more serious psoriasis-like diseases than wide type mice after treating with IMQ.The elevation of IL-30 in serum could explain this result.In order to define the IL-30 mechanism in the treating of psoriasis,we studied the biological pathways of IL-30.Results showed that IL-30 could active STAT3 pathway,induce the expression of SOCS3 and inhibit the excessive phosphorylation of STAT3..Meanwhile,IL-30 could restrain the NF-?B pathway effectively.To sum up,IL-30 could restrain Th1 and Th17 cells differentiation at the same time.It also could cut off the relationship between innate immune and adaptive immune through decreasing the antigen presenting ability of DCs.This study illustrates that IL-30 can be applied to treating psoriasis and other autoimmune diseases due to its various function on immune.