IL-22 Antibody Attenuates Acute Graft-versus-host Disease Via CD11b~+ Cells Increasing Foxp3~+ T Cells

Background:The transfer of splenocytes isolated from B6 mice into normal B6D2F1 mice induces acute graft-versus-host disease (aGVHD), which is mediated by the elimination of recipient B lymphocytes by donor cytotoxic T cells. IL-22 is a cytokine that is structurally related to IL-10 and is secreted by Thl cells, Thl7 cells and innate immune cells.Objective:To investigate the association between IL-22 and aGVHD, anti-mouse IL-22 antibody (IL-22 Ab) was used to ablate the activity of this cytokine in a mouse model of aGVHD.Methods:Using IL-22 antibody treated experimental group and the control IgG treated group of mice treated aGVHD, compare the change of host cells and donor cells, proinflammatory and anti-inflammatory cytokine secretion, CD4+ Foxp3 cell percentage change in IL-22ab treatment and IgG treatment aGVHD mice.Results:Our results proved that administration of IL-22 Ab significantly reduced the progression of aGVHD in B6D2F1 recipients of B6 grafts. In addition, IL-22 Ab treatment decreased the percentage of interferon-y+(IFN-y) and tumor necrosis factor-α+(TNF-a) T cells but increased the numbers of forkhead box p3+regulatory T cells (Tregs) in vivo. In the presence of Tregs and donor CD11b+ cells, IL-22Ab protected against aGVHD. Furthermore, the process of Tregs induction was more efficient when CD4+CD62L+ T cells were differentiated in the presence of CD 11 b+ cells obtained from IL-22Ab-treated aGVHD mice compared to untreated control cell co-culture. Finally, IL-22Ab regulated the expression of cytokines and co-stimulatory molecules of CD11b+ cells in aGVHD.Conclusions:IL-22 antibody attenuates acute graft-versus host disease via increasing Foxp3+ T cells through modulating the function of CDllb+cells and represent a valid approach towards aGVHD prevention.