ILC2 Proliferated By IL-33 Stimulation Alleviates Acute Colitis In Rag1^-/-Mouse Through Promoting M2 Macrophage Polarization

Objective:Inflammatory bowel disease?IBD?is an autoimmune disease that is mainly caused by chronic inflammatory damage.The disease can affect the ileum,rectum and colon.IBD includes ulcerative colitis?UC?and Crohn's disease?CD?.Its pathogenesis has not been fully understood.It is generally believed that it is closely related to immune system abnomity.Recent years,there have been a lot of related researches on IBD.But because of its complicated pathogenesis,the treatments for IBD are limited,mainly anti-inflammatory and immunosuppressive drugs.IL-33 is a member of the IL-1 family.It mainly exists in epithelial cells and endothelial cells.It is released as a alarmin to various tissues in the event of tissue damage and pathogen invasion,activating downstream immune cells to produce various biological effects.There have been many studies on the role of IL-33 in IBD,but because of the diverse roles of IL-33,the mechanism of IL-33 is still not fully understood.ILC2 is one of the target cells of IL-33.The role of ILC2 in airway hyperresponsiveness has discussed extensively.But there were few reports in the study of IBD.ILC2 is similar to TH2cells which produce TH2 cytokines such as IL-4,IL-5 and IL-13.Both also highly express the transcription factor GATA-3.TH2 cells play an important role in IBD.Thus we assume ILC2 also plays an important role in IBD.The research on the mechanism of ILC2 functions in IBD could be of great significance.Methods:We first injected rIL-33 into C57/BL6 mice by intraperitoneal injection,and made single-cell suspensions of mouse LPL,MLN,spleen,and lung.After confirming that IL-33 can cause ILC2 proliferation,further explore the cell surface markers and cytokines expressed by activated ILC2.After that,primary ILC2 cells of C57/BL6 mice were sorted out and adoptive transferred to Rag1-/-mice.DSS was administrated to induce acute colitis in Rag1-/-mice.H&E staining was used to evaluate ILC2 effect on Rag1-/-mice acute colitis.Finally,the possibility mechanism of ILC2 in IBD was further explored by ELISA and flow cytometry.Results:?1?In LPL,MLN,spleen and lung,IL-33 can significantly promote ILC2proliferation.?2?The proliferation of IL-33 on ILC2 reached its peak on day 5.?3?Under the activation of IL-33,ILC2 in LPL and MLN expressed a large amount of IL-5 and IL-13,and a small amount of IL-4 was expressed in LPL.?4?ILC2 plays a protective role in DSS-induced acute colitis in Rag1^-/-mice.?5?ILC2 can significantly increase the expression of IL-13 and IL-5 in Rag1^-/-mice LPL.?6?ILC2 can increase the number of M2 macrophages in Rag1^-/-mice LPL.Conclusion:?1?Intraperitoneal injection of rIL-33 can cause the proliferation of mouse LPL,MLN,spleen and lung.?2?Under the stimulation of rIL-33,ILC2 can produce a large amount of IL-5,IL-13 and a small amount of IL-4 in LPL.ILC2 can produce a large amount of IL-5 and IL-13 in MLN.?3?ILC2 proliferated under IL-33stimulation can significantly improve DSS-induced acute inflammatory bowel disease through adoptive transfer to Rag1-/-mice;?4?ILC2 can cause macrophages polarize to M2 Macrophage.