Induced SHIP Deficiency Expands Myeloid Regulatory Cells and Abrogates Graft-versus-Host Disease

• DOI: 10.4049/jimmunol.178.5.2893
• Publication Date: 2014-04-18T17:14:39Z
• Authors: Kim H. T. Paraiso; Tomar Ghansah; Amy Costello; Robert W. Engelman; William G. Kerr
• Keywords: 0301 basic medicine; T-Lymphocytes; Inositol Polyphosphate 5-Phosphatases; Graft vs Host Disease; Mice, Transgenic; Phosphoric Monoester Hydrolases; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Acute Disease; Animals; Homeostasis; Humans; Transplantation, Homologous; Lymph Nodes; Myeloid Progenitor Cells; Spleen; Bone Marrow Transplantation

Abstract Graft-vs-host disease (GVHD) is the leading cause of treatment-related death in allogeneic bone marrow (BM) transplantation. Immunosuppressive strategies to control GVHD are only partially effective and often lead life-threatening infections. We previously showed that engraftment MHC-mismatched BM enhanced abrogated recipients homozygous for a germline SHIP mutation. In this study, we report development genetic model which deficiency can be induced adult mice. Using model, show induction mice leads rapid significant expansion myeloid suppressor cells peripheral lymphoid tissues. Consistent with cells, splenocytes lymph node from significantly compromised their ability prime T cell responses. These results demonstrate regulates homeostatic signals these immunoregulatory physiology. findings, before receiving cell-replete graft abrogates acute GVHD. findings indicate target could increase efficacy utility transplantation, thereby provide curative therapy wide spectrum human diseases.