Oncotarget

Research Papers: Immunology:

CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice

Sun Mi Gu, Mi Hee Park, Hyung Mun Yun, Sang Bae Han, Ki Wan Oh, Dong Ju Son, Jae Suk Yun and Jin Tae Hong _

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Oncotarget. 2016; 7:15382-15393. https://doi.org/10.18632/oncotarget.8097

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Abstract

Sun Mi Gu1,*, Mi Hee Park1,*, Hyung Mun Yun2, Sang Bae Han1, Ki Wan Oh1, Dong Ju Son1, Jae Suk Yun3 and Jin Tae Hong1

1 College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, Republic of Korea

2 Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea

3 Pharmacological Research Division, National Institute of Food and Drug Safety Evaluation (NIFDS), Ministry of Food and Drug Safety (MFDS), Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, Republic of Korea

* These authors have contributed equally to this work

Correspondence to:

Jae Suk Yun, email:

Jin Tae Hong, email:

Keywords: multiple sclerosis; C-C chemokine receptor 5; cytokine; chemokine; experimental autoimmune encephalomyelitis; Immunology and Microbiology Section; Immune response; Immunity

Received: August 30, 2015 Accepted: February 28, 2016 Published: March 15, 2016

Abstract

Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5-/-) mice. CCR5-/- and CCR5+/+ (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5-/- mice than CCR5+/+ mice. Immune cells (CD3+, CD4+, CD8+, B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5-/- mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5-/- mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5-/- mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.


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