Radiation and host retinoic acid signaling promote the induction of gut-homing donor T cells after allogeneic hematopoietic stem cell transplantation.

Intestinal graft-versus-host disease (GVHD) remains a devastating complication after allogeneic hematopoietic stem cell transplantation (HSCT). Although it has been well established that gut-tropic donor T cells expressing integrin α4β7 are required to cause intestinal damage, the factors that control the induction of this pathogenic T cell population remain to be identified. Retinoic acid (RA) plays an important role in inducing α4β7 expression on T cells.

Effects of Donor Vitamin A Deficiency and Pharmacologic Modulation of Donor T Cell Retinoic Acid Pathway on the Severity of Experimental Graft-versus-Host Disease.

Graft-versus-host disease (GVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). A combination of genetic and nongenetic factors dictates the incidence and severity of GVHD. Recent studies have identified the potential role of the retinoic acid (RA)/retinoic acid receptor (RAR) pathway in the pathogenesis of GVHD.

Circadian genes, xBmal1 and xNocturnin, modulate the timing and differentiation of somites in Xenopus laevis.

We have been investigating whether xBmal1 and xNocturnin play a role in somitogenesis, a cyclic developmental process with an ultradian period. Previous work from our lab shows that circadian genes (xPeriod1, xPeriod2, xBmal1, and xNocturnin) are expressed in developing somites. Somites eventually form the vertebrae, muscles of the back, and dermis.

A critical role for the retinoic acid signaling pathway in the pathophysiology of gastrointestinal graft-versus-host disease.

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 α4β7, 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.