BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graft-versus-host disease

The contribution of cytokine signals, autophagy and antigen presentation to complications associated with allogeneic stem cell transplantation

“…Although studies have demonstrated that c cytokines are elevated after allogeneic SCT, little has been addressed regarding the role for these cytokines in GVHD responses [33,280,284,293]. Here we show a protective role for c cytokine signalling in the recipient following allogenetic SCT.…”

“…Our studies demonstrate that c signalling in the donor T cell compartment is unequivocally pathogenic. This is particularly interesting considering that although Csf2 is indeed produced by pathogenic T cells during GVHD [171,280] and transgenic overexpression of Csf2 in T cells leads to increased inflammatory infiltrate and cytokine production [175], T cells are largely considered to lack expression of the Csf2R receptor [173,174]. Although we have identified that functional signalling in donor T cells is pathogenic in both acute and chronic GVHD models, the mechanism by which c signalling in the donor compartment is eliciting pathogenicity remains to be elucidated.…”

“…Csf2 is produced by multiple cell types including those of the haematopoietic lineage: macrophages, fibroblasts, neutrophils, eosinophils, ILC and T cells but additionally by nonhaematopoietic epithelial cells, mesothelial cells, chondrocytes and Paneth cells [279]. In the setting of GVHD subsets of CD4 and CD8 T effector cells produce Csf2 after transplant [172] and these Csf2 + T cells were recently shown to be critical promoters of intestinal inflammation in GVHD [280]. Csf2 is produced by both haematopoietic and Although T cells contained within the donor graft are established critical mediators of both the acute and chronic forms of GVHD, it is increasingly appreciated that multiple myeloid populations contribute to GVHD pathophysiology.…”

“…Csf2 is produced by both haematopoietic and stromal cells in non-lymphoid tissues in the steady state and is established as a critical growth factor for the development of multiple myeloid populations including immature myeloid precursors and mature myeloid DC [127,169,170,194,279,287,288]. In the setting of GVHD subsets of CD4 and CD8 T effector cells produce Csf2 after transplant [171,172] and these Csf2 + T cells were recently shown to be critical promoters of intestinal inflammation in GVHD [280]. Thus Csf2 is a potent cytokine for the development and function of myeloid populations that play critical roles in inflammatory responses including GVHD.…”

“…Elevated IL-5 has been reported during aGVHD and proposed as a sensitive diagnostic marker for the disease [293]. More recently, studies have identified elevated Csf2 during the early stages of GVHD produced by a pathogenic effector T cell population reported to be critical for the promotion of intestinal GVHD inflammation [33,280]. Intriguingly, Csf2 and IL-5 together with IL-3, signal through a common c receptor subunit and are thus known as the c family cytokines [133].…”