Contents lists available at ScienceDirect Cytokine journal homepage: www.elsevier.com/locate/cytokine Frequencies of IL-15Rα+ cells in patients with Behçet’s disease and the effects of overexpressing IL-15Rα+ on disease symptoms in mice S.M. Shamsul Islam a , Bunsoon Choi b , Juyoung Choi a , Eun-So Lee c, ⁎ , Seonghyang Sohn a,b, ⁎ a Department of Biomedical Science, Ajou University School of Medicine, Suwon 16499, Republic of Korea b Department of Microbiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea c Department of Dermatology, Ajou University School of Medicine, Suwon 16499, Republic of Korea ARTICLE INFO Keywords: IL-15Rα IL-15/IL-15Rα-Fc protein complex Inflammation Behçet's disease HSV Mouse model ABSTRACT It has been suggested higher serum levels of IL-15 and lower expression levels of IL-15 receptor alpha (IL-15Rα) are correlated with pathogenesis of Behçet's disease (BD). However, whether overexpressing IL-15Rα could be used as a therapeutic candidate for BD is currently unclear. Therefore, the purpose of this study was to determine whether overexpressing IL-15Rα could affect BD symptoms in a mouse model. IL-15/IL-15Rα complex expres- sing vector or protein complex of IL-15/IL-15Rα-Fc was used to treat BD mice. Frequencies of IL-15Rα+ cells in peripheral blood leukocytes (PBL) and lymph node cells were determined using a flow cytometer. BD symptoms in mice improved after treatment with IL-15/15Rα expression vector or IL-15/IL-15Rα-Fc protein complex. In addition, treatment with pIL-15/15Rα significantly (p = .016) decreased disease severity score of BD mice compared to treatment with control vector. Frequencies of IL-15Rα+ cells were also significantly (p = .01) higher in peritoneal macrophages of pIL-15/15Rα treated BD mice than those of mice treated with control vector. Frequencies of IL-15Rα+ PBL were also significantly higher in BD mice treated with IL-15/IL-15Rα-Fc protein complex than those in the control group. These results suggest up-regulating IL-15Rα+ cells could be used as novel therapeutic strategies to control BD in the future. 1. Introduction Behcet's disease (BD) is a chronic multi-systemic inflammatory disease presented by oral ulcer, genital ulcer, skin ulcer, and ocular inflammation. BD frequently involves joints, intestine, and the central nervous system [1]. Its pathogenic mechanism remains elusive. How- ever, viral, genetic, and immunological factors are likely to be involved [2]. Viral hypothesis is based on the detection of viruses in saliva and oral tissues from BD patients with ulcer [3,4]. ICR mice inoculated with herpes simplex virus (HSV) has been developed as an animal model showing BD-like symptoms such as oral ulcers, genital ulcer, skin ul- cers, eye symptoms, intestinal ulcers, arthritis, neural involvement, and skin crust [5]. It has been suggested that HSV might play an important role in the pathogenesis in BD patients [6] and BD model mice [5]. HSV-1 DNA and higher serum antibodies against HSV have been re- ported in BD patients than those in normal controls [7,8]. Interleikin-15 (IL-15) is a pleiotropic proinflammatory cytokine produced by activated dendritic cells, macrophages, and monocytes [9–11] essential for cell survival, cell proliferation, and functional ac- tivity of immune cells such as natural killer (NK) cells, memory T cells, monocytes, macrophages, and dendritic cells. IL-15 stimulates B cells to proliferate and secrete immunoglobulins [12,13]. IL-15 is also involved in the pathogenesis of diverse inflammatory diseases including BD [14]. IL-15 exerts its effect by binding to a membrane receptor composed of high affinity binding alpha chain (IL-15Rα) [15] that forms a hetero- trimeric receptor complex with IL-15Rβ and IL-15Rγ [16]. IL-15Rα is expressed independently of IL-15Rβγ in humans and mice [17]. IL- 15Rα restricts aberrant immune stimulation and decreases the risk of uncontrolled IL-15 exposure [18]. IL-15Rα chain serves as a protector in the cell membrane. The importance of IL-15 for the production and survival of memory CD8 T cells has been shown using virus infected IL- 15 knockout mice [19,20]. It has been reported that the combination of human IL-15 and mouse IL-15Rα-Fc results in significant proliferation of NK cells and NKT cells in mouse in vivo [21]. Higher expressions of IL-15 have been observed in serum, cere- brospinal fluid, and aqueous humor of BD patients [22–24]. However, whether overexpressing IL-15Rα could be used as a treatment for BD is currently unclear. Therefore, the purpose of this study was to determine whether overexpressing IL-15Rα could affect BD symptoms in a mouse model. https://doi.org/10.1016/j.cyto.2018.01.010 Received 24 November 2017; Received in revised form 5 January 2018; Accepted 10 January 2018 ⁎ Corresponding authors at: Department of Biomedical Science, Ajou University School of Medicine, Suwon 16499, Republic of Korea and Department of Microbiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea (S. Sohn). E-mail addresses: esl@ajou.ac.kr (E.-S. Lee), sohnsh@ajou.ac.kr (S. Sohn). Cytokine xxx (xxxx) xxx–xxx 1043-4666/ © 2018 Elsevier Ltd. All rights reserved. Please cite this article as: Shamsul Islam, S.M., Cytokine (2018), https://doi.org/10.1016/j.cyto.2018.01.010