Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells

Abstract

Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological phototherapy. As for the application of NB-UVB phototherapy to graft-versus-host disease (GVHD), we previously reported that it was highly efficacious for cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg) cells induced by NB-UVB might be one of the mechanisms. In order to examine whether NB-UVB irradiation through expansion of Treg cells is effective for the treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the intestine or liver, we conducted experiments in which a murine lethal aGVHD model, characterized by severe involvement of the intestine, was irradiated with NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival rate. The pathological score of aGVHD was improved in all affected organs: intestine, liver, and skin. In the serum of mice irradiated with NB-UVB, the levels of Treg cells-associated cytokines such as transforming growth factor beta (TGFβ) and interleukin-10 (IL-10) were elevated. The numbers of infiltrating Treg cells in inflamed tissue of the intestine and those in spleen were increased in mice treated with NB-UVB. This is the first report demonstrating that NB-UVB phototherapy has the ability to ameliorate intestinal aGVHD through the expansion of Treg cells.

Regulatory B cells induced by ultraviolet B through toll‐like receptor 4 signalling contribute to the suppression of contact hypersensitivity responses in mice

“…UVB‐induced regulatory T cells have been widely considered to mediate UVB‐induced immunosuppression by inhibiting T effector cells (–). However, because of the lack of regulatory T cell depletion experiments in our study, we cannot exclude a suppressive role of regulatory T cells in our research model.…”

From Early Immunomodulatory Triggers to Immunosuppressive Outcome: Therapeutic Implications of the Complex Interplay Between the Wavebands of Sunlight and the Skin

“…In mastocytosis, phototherapy might act by direct cytotoxicity against activated mast cells and by stabilizing mast cells, thus inhibiting them from releasing soluble proinflammatory mediators such as histamine ( 89 ). In graft vs. host disease (GVHD), the predominant mechanism of action may be immunomodulation by downregulating the activity of grafted cells against the host ( 90 ). The effect of OVB in pruritus remains entirely elusive at the moment; however, a halfside comparison study implied a systemic effect, since treatment reduced pruritus not only on the irradiated body half but also to an equal degree on the unirradiated side ( 91 ).…”

Treatment rationale and design of a phase II study of narrow-band ultraviolet B phototherapy for cutaneous steroid-refractory acute graft-vs-host disease following allogenic stem-cell transplantation

“…[14,19] Iyama et al showed that NB-UVB treatment expanded CD4 + CD25 + Foxp3 + regulatory T cells in peripheral blood of patients with cutaneous aGVHD, and NB-UVB-induced regulatory T cells may be functional in the skin and intestine or liver, based on a mouse model of aGVHD. [20] It is unknown if a systemic increase of regulatory T cells impairs the GVT effect and increases the risk for relapse, [11] which emphasizes the need to be cautious about relapse of underlying hematologic malignancy. In addition, use of NB-UVB has occasionally been associated with emergence of cutaneous cancers, especially in immunocompromised patients, and GVHD itself may increase the risk of melanoma and nonmelanoma skin cancer.…”