Study On The Role Of Th22Cells And Its Functional Cytokine IL-22in Systemic Autoimmune Diseases

Background: Systemic autoimmune disease refers to the body immune responses toself-antigens and lead to multiple organ and system damage. Rheumatoid Arthritis(RA) andSystemic Lupus Erythematosus(SLE)are two kinds of the most common and typical systemautoimmune disease. RA can cause symmetric multi-joint synovitis, the destruction ofarticular cartilageand joint space narrowing, terminal can appear deformity of joints. Thedisease,which caused great economic burden to society and family,is the primary disease thatcaused loss of labor ability and disability in China.SLE is a diffuse and systemicautoimmune disease, resulting in a lot of autoantibody deposition, complement activationand immune complexes. The prevalence and mortality rate of the disease is high. SLE hasbecome a public health problem in society. At present, the pathogenesis of SLE and RA isstill not completely clear, leading to the difficulty in treatment.Aim: To study the expressions of Th22cells and its functional cytokines IL-22indifferent stages of RA and SLE as represented systemic autoimmune diseases.And thenexplore its role in the pathogenesis of systemic autoimmune disease, provide new ideas forthe early diagnosis and treatment of these diseases.Method:The frequencies of peripheral blood Th22,IL-22~+Th17,IL-22~+Th1,Th17cells and the concentrations of serum IL-22,IL-17and IFNγin RA,SLE patients and healthycontrols (HC) were characterized by flow cytometry analysis and enzyme Alliance immuneadsorption test (ELISA). The potential association of the frequency of T cells and cytokineswith clinical measures was analyzed. The effects of Methotrexate combined withleflunomide treatment in RA and methylprednisolone combined with cyclophosphamide,hydroxychloroquine treatment in SLE on the frequency of these cells and cytokines weredetermined. The levels of serum anti-dsDNA and anti-Sm were determined by indirectimmunofluorescence.The concentrations of serum C3, C4,erythrocyte sedimentation rate(ESR), rheumatoid factor (RF)and CRP were determined by scatter turbidimetry.The levelsof serum anticyclic citrullinated peptide antibody (CCP) were determined by thechemoluminescence microparticle immune method.Results:1.The frequencies of peripheral blood Th22,IL-22~+Th17,IL-22~+Th1, Th17cellsand the concentrations of serum IL-22,IL-17in RA and SLE patients were siginificantlyhigher than that in healthy controls. The concentration of serum IFN-γ was also higher thanthat in healthy controls.2. A statistically significant positive correlation was found between the percentage ofIL-22~+Th17and Th22cells in RA and SLE. The percentage of IL-22~+Th17cells waspositivly correlated with Th17cells in RA patients. The percentage of Th22cells waspositivly correlated with Th17cells in SLE patients.3. A statistically significant positive correlation was found between the percentage of IL-22+CD4+T cells and DAS28. The percentages of Th22and Th17cells were positivlycorrelated with erythrocyte sedimentation rate（ESR）. The percentage of Th17cells werepositivly correlated with rheumatoid factor.4. A significant positive correlation was found between the percentage of IL-22~+CD4~+Tor Th17cells and SLEDAI in SLE patients. The percentage of Th22cells were significantlyassociated with facial erythema, alopecia or ANA-positive expression in SLE. Thepercentage of Th17cells were significantly associated with anti-dsDNA-positive orphotoallergy.5. The methotrexate combined with Leflunomide treatment for12weeks reduced thefrequencies of Th22,IL-22~+Th17and Th17cells and the concentrations of IL-22,IL-17andIFNγin drug response RA patients.6. The methylprednisolone combined with cyclophosphamide, hydroxychloroquinetreatment for4weeks reduced the frequencies of Th22,IL-22~+Th17and Th17cells and theconcentrations of IL-22and IL-17in drug response SLE patients.Conclusions:1. The IL-22~+CD4~+T mainly Th22cells and IL-22may play an importantrole in the pathogenesis of RA and SLE,and as bio-indicators for monitoring disease severityand drug efficacy.2. There is a positive correlation between Th22and Th17cells(including IL-22~+andIL-22-Th17cells) in RA and SLE patients,suggesting that Th22and Th17cells may play asynergistic role in these two kinds of autoimmune diseases. 3. The pathogenesis of SLE Patients with different clinical and laboratory features maynot be the same, treatment may also need individual.4. Corticosteroids and immunosuppressive drugs may be play roles in the treatment ofsystemic autoimmune disease by regulating the expression of lymphocyte subsets andcytokine, further regulation of the immune status.5. This subject understanding changes of the expression of Th22cells and IL-22beforeand after treatment in in patients with RA and SLE, and further defined the pathogenesis forthese two types of autoimmune disease.In the near future we can change the abnormalimmune status of the patients by regulating the Th22cells and IL-22and provide newtherapeutic targets for prevention and treatment of diseases.