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

Akari Hashimoto,Shingo Ichimiya,Ayumi Tatekoshi,Masayoshi Kobune,Koji Miyanishi,Soushi Ibata,Yusuke Kamihara,Kazuyuki Murase,Masahiro Yoshida,Yutaka Kawano,Hiroto Horiguchi,Satoshi Iyama,Junji Kato,Kohichi Takada,Tsutomu Sato,Andrzej T Slominski

doi:10.1371/journal.pone.0152823

Akari Hashimoto, Shingo Ichimiya + Show 14 more

Open Access

https://doi.org/10.1371/journal.pone.0152823

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Journal: PLOS ONE	Publication Date: Mar 31, 2016
Citations: 8	License type: CC BY 4.0

Affiliation: Sapporo Medical University

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.

Highlights

Allogeneic hematopoietic stem cell transplantation is an effective treatment for various malignant and nonmalignant hematologic disorders
A second group of mice treated with total body irradiation (TBI)/bone marrow transplantation (BMT) was irradiated with Narrowband ultraviolet B (NB-UVB) three times a week starting on day 13, just before the start of bloody diarrhea (“TBI/BMT+NB-UVB” group)
As for the application of NB-UVB phototherapy to graft-versus-host disease (GVHD), we and others have reported that it was highly efficacious for cutaneous lesions of both acute and chronic GVHD [11,12,13,14,15,16]

Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for various malignant and nonmalignant hematologic disorders. Graft-versus-host disease (GVHD) remains a life-threatening complication of allo-HSCT [1]. NB-UVB Ameliorates Gut Acute GVHD by Treg Cells (aGVHD), a leading cause of nonrelapse mortality after allo-HSCT, is characterized by dysfunction in three organ systems: the skin, liver, and gastrointestinal (GI) tract [2]. Corticosteroids are the cornerstone of initial therapy for aGVHD, leading to complete response in 25%-69% of patients [3,4,5,6,7]. Patients not responding to steroids have a dismal prognosis, with poor survival [3,8]. Numerous agents for treating steroid-refractory aGVHD have been studied [8,9]; to date, there is no consensus for the treatment of refractory aGVHD [10]

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