| First Author | Chen X | Year | 2013 |
| Journal | Blood | Volume | 121 |
| Issue | 19 | Pages | 3970-80 |
| PubMed ID | 23529927 | Mgi Jnum | J:198223 |
| Mgi Id | MGI:5495874 | Doi | 10.1182/blood-2012-08-445130 |
| Citation | Chen X, et al. (2013) A critical role for the retinoic acid signaling pathway in the pathophysiology of gastrointestinal graft-versus-host disease. Blood 121(19):3970-80 |
| abstractText | Damage to the gastrointestinal tract during graft-versus-host disease (GVHD) is one of the major causes of morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. In the current study, we identified a critical role for the retinoic acid (RA) signaling pathway in the induction and propagation of gastrointestinal GVHD. The administration of exogenous RA significantly increased expression of the gut-homing molecules, CCR9 and alpha4beta7, on donor T cells in mesenteric lymph nodes, and augmented the accumulation of proinflammatory CD4(+) and CD8(+) T cells within the gut mucosa, leading to a selective exacerbation of colonic GVHD and increased overall mortality. Conversely, depletion of RA in recipient mice by vitamin A deprivation resulted in a dramatic reduction of gut-homing molecule expression on donor T cells after HSCT. Significantly, absence of the RA receptor-alpha on donor T cells markedly attenuated the ability of these cells to cause lethal GVHD. This observation was attributable to a significant reduction in pathological damage within the colon. These findings identify an organ-specific role for RA in GVHD and provide evidence that blockade of the RA signaling pathway may represent a novel strategy for mitigating the severity of colonic GVHD. |
