CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4+Foxp3+ T and IL-17+CD4+ Th17 cells

• DOI: 10.1186/s12974-016-0656-x
• Publication Date: 2016-07-20T10:02:02Z
• Authors: Jin Hyoung Kim; Ajit Mahadev Patil; Jin Young Choi; Seong Bum Kim; Erdenebelig Uyangaa; Ferdaus Mohd Alta...; Sang-Youel Park; John Hwa Lee; Seong Kug Eo
• Keywords: Adoptive Cell Transfer; CCL5; Viral encephalitis

CCR5 is a CC chemokine receptor involved in the migration of effector leukocytes including macrophages, NK, and T cells into inflamed tissues. Also, role CD4+Foxp3+ regulatory cell (Treg) homing has recently begun to grab attention. Japanese encephalitis (JE) defined as severe neuroinflammation central nervous system (CNS) following infection with mosquito-borne flavivirus JE virus. However, potential contribution progression via mediating Treg not been investigated. Infected wild-type (Ccr5+/+) CCR5-deficient (Ccr5−/−) mice were examined daily for mortality clinical signs, CNS was evaluated by infiltration inflammatory cytokine expression. In addition, viral burden, NK- JEV-specific responses analyzed. Adoptive transfer CCR5+CD4+Foxp3+ Tregs used evaluate progression. ablation exacerbated without altering burden extraneural tissues, manifested increased Ly-6Chi monocytes Ly-6Ghi granulocytes. Compared Ccr5+/+ mice, Ccr5−/− unexpectedly showed IFN-γ+NK CD8+ spleen, but CD4+ cells. More interestingly, CCR5-ablation resulted skewed response IL-17+CD4+ Th17 correspondingly reduced spleen brain, which closely associated JE. Our results also revealed that adoptive sorted could ameliorate apparently cells, myeloid-derived Instead, expression anti-inflammatory cytokines (IL-10 TGF-β) transferred CCR5+ found produce IL-10. regulates governing timely appropriate Tregs, thereby facilitating host survival. Therefore, this critical extended raises possible safety concerns regarding use antagonists human immunodeficiency virus (HIV)-infected individuals who inhabit regions both HIV flaviviruses, such JEV West Nile virus, are endemic.