| First Author | Okiyama N | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 4 | Pages | 992-1000 |
| PubMed ID | 24213371 | Mgi Jnum | J:207941 |
| Mgi Id | MGI:5559965 | Doi | 10.1038/jid.2013.476 |
| Citation | Okiyama N, et al. (2014) Reversal of CD8 T-Cell-Mediated Mucocutaneous Graft-Versus-Host-Like Disease by the JAK Inhibitor Tofacitinib. J Invest Dermatol 134(4):992-1000 |
| abstractText | The utility of allogeneic hematopoietic stem cell transplantation is limited by graft-versus-host disease (GVHD), a significant cause of morbidity and mortality. Patients with GVHD exhibit cutaneous manifestations with histological features of interface dermatitis followed by scleroderma-like changes. JAK inhibitors represent a class of immunomodulatory drugs that inhibit signaling by multiple cytokines. Herein we report the effects of tofacitinib in a murine model of GVHD. Oral administration of tofacitinib prevented GVHD-like disease manifested by weight loss and mucocutaneous lesions. More importantly, tofacitinib was also effective in reversing established disease. Tofacitinib diminished the expansion and activation of murine CD8 T cells in this model, and had similar effects on IL-2-stimulated human CD8 T cells. Tofacitinib also inhibited the expression of IFN-gamma-inducible chemoattractants by keratinocytes, and IFN-gamma-inducible cell death of keratinocytes. Tofacitinib may be an effective drug for treatment against CD8 T-cell-mediated mucocutaneous diseases in patients with GVHD. |
