Helper Innate Lymphoid Cells in Allogenic Hematopoietic Stem Cell Transplantation and Graft Versus Host Disease

Abstract

Helper Innate Lymphoid Cells (hILCs), including ILC1s, ILC2s, and ILC3s, are mainly localized at the mucosal barriers where they play an important role in tissue regeneration and homeostasis through the secretion of specific sets of cytokines. The recent identification of a circulating ILC precursor able to generate all ILC mature subsets in physiological conditions, suggests that "ILC-poiesis" may be important in the context of hematopoietic stem cell transplantation (HSCT). Indeed, in HSCT the conditioning regimen (chemotherapy and radiotherapy) and Graft vs Host Disease (GvHD) may cause severe damages to mucosal tissues. Therefore, it is conceivable that rapid reconstitution of the hILC compartment may be beneficial in HSCT, by promoting mucosal tissue repair/regeneration and providing protection from opportunistic infections. In this review, we will summarize the evidence for a role of hILCs in allogenic HSCT for the treatment of hematological malignancies in all its steps, from the preparative regimen to the immune reconstitution in the recipient. The protective properties of hILCs at the mucosal barrier interfaces make them an attractive target to exploit in future cellular therapies aimed at improving allogenic HSCT outcome.

Ruxolitinib, a JAK1/JAK2 Selective Inhibitor, Ameliorates Acute and Chronic Steroid-Refractory Gvhd Mouse Models

“…Pharmacological targeting of the JAK-STAT pathway was significantly efficacious in both the acute and chronic GvHD preclinical models tested. However, several pathological mechanisms utilize downstream signaling pathways that are potentially JAK-STAT-independent [29,31,32]. In human cGvHD, alloreactive B-cell responses are associated with elevated B-cell activating factor levels and activation of Bruton tyrosine kinase, spleen tyrosine kinase and B-cell linker [33].…”

Immune processes in the pathogenesis of chronic lung allograft dysfunction: identifying the missing pieces of the puzzle

“…[92,93]. As such, it does not seem unlikely that they contribute to the pathogenesis of CLAD, and further investigation is warranted [94][95][96].…”

Cascade of Inflammatory, Fibrotic Processes, and Stress-Induced Senescence in Chronic GVHD-Related Dry Eye Disease

“…Studies have shown that type 2 innate lymphoid cells (ILC2s) recruit myeloid-derived suppressor cells that suppress T cell-mediated GVHD and ILC3s secreting IL-22, enhancing intestinal stem cell function, promoting repair and the release of adenosine and suppressing T cell proliferation [ 61 , 62 , 63 , 64 , 65 ]. It is likely that an altered or reduced number of ILCs play some role under allogeneic circumstances of the ocular surface of dry eye associated with cGVHD.…”