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Japanese encephalitis (JE) is neuroinflammation characterized by uncontrolled infiltration of peripheral leukocytes into the central nervous system (CNS). We previously demonstrated exacerbation of JE following CD11c hi dendritic cell (DC) ablation in CD11c-DTR transgenic mice. Moreover, CD11c hi DC ablation led to abnormal differentiation of CD11b + Ly-6C hi monocytes and enhanced permeability of the blood-brain barrier (BBB), resulting in promoting the progression of JE. Here, we examined changes in lymphoid and myeloid-derived leukocyte subpopulations associated with pro- and anti-inflammation during JE progression. The analyses of this study focused on regulatory CD4 + Foxp3 + regulatory T cells (Tregs), IL-17 + CD4 + Th17 cells, and CD11b + Ly-6C hi and Ly-6C lo monocytes. CD11c hi DC ablation resulted in the accumulation of IL-17 + CD4 + Th17 cells in the CNS, thereby leading to lower ratio of Tregs to Th17 cells. This result was corroborated by the higher expression levels of IL-17 and RORγT in CD4 + T cells from the brains of CD11c hi DC-ablated mice. In addition, CD11c hi DC-ablated mice showed higher frequency and total number of inflammatory CD11b + Ly-6C hi monocytes, whereas CD11b + Ly-6C lo monocytes were detected with lower frequency and total number in CD11c hi DC-ablated mice. Furthermore, CD11c hi DC ablation altered the phenotype and function of CD11b + Ly-6C lo monocytes, resulting in lower levels of activation marker and anti-inflammatory cytokine (IL-10 and TGF-β) expression. Collectively, these results indicate that CD11c hi DC ablation caused an imbalance in CD4 + Th17/Treg cells and CD11b + Ly-6C hi /Ly-6C lo monocytes in the lymphoid tissue and CNS during JE progression. This imbalanced orchestration of pro- and anti-inflammatory leukocytes following CD11c hi DC ablation may contribute to the exacerbation of JE.

immune network/immune network

Exacerbation of Japanese Encephalitis by CD11chi Dendritic Cell Ablation Is Associated with an Imbalance in Regulatory Foxp3+ and IL-17+CD4+ Th17 Cells and in Ly-6Chi and Ly-6Clo Monocytes