Choroid plexus-selective inactivation of adenosine A2A receptors protects against T cell infiltration and experimental autoimmune encephalomyelitis

• DOI: 10.1186/s12974-022-02415-z
• Publication Date: 2022-02-18T07:10:54Z
• Authors: Wu Zheng; Yijia Feng; Zhenhai Zeng; Mengqian Ye; Mengru Wang; Xin Liu; Ping Tang; Huiping Shang; Xiaoting Sun; Xiangxiang Lin; Muran Wang; Zhengzheng Li; Yiyun Weng; Wei Guo; Sergii Vakal; Jiang-fan Chen
• Keywords: Adenosine A2A receptor; Myelin oligodendrocyte glycoprotein; Encephalomyelitis

Abstract Background Multiple sclerosis (MS) is one of the most common autoimmune disorders characterized by infiltration immune cells into brain and demyelination. The unwanted immunosuppressive side effect therapeutically successful natalizumab led us to focus on choroid plexus (CP), a key site for first wave cell in experimental encephalomyelitis (EAE), control trafficking. Adenosine A 2A receptor (A R) emerging as potential pharmacological target EAE pathogenesis. However, cellular basis R-mediated protection remains undetermined. Methods In model, we assessed R expression leukocyte trafficking determinants CP immunohistochemistry qPCR analyses. We determined antagonist KW6002 treatment at days 8–12 or 8–14 post-immunization T across pathology. critical role CP-A pathology focal knock-down via intracerebroventricular injection CRE-TAT recombinase flox/flox mice. cultured epithelium, also evaluated overexpression Rs agonist CGS21680 permeability lymphocytes migration. Results found specific upregulation associated with enhanced gateway activity peaked day 12 Furthermore, reduced attenuated Importantly, pathogenic Th17 + inhibiting CCR6–CCL20 axis through NFκB/STAT3 pathway protected against Lastly, activation epithelium increased facilitated Conclusion These findings define niche primary sites action, whereby antagonists confer Thus, targeting represents novel therapeutic strategy MS controlling CP.