Exacerbation of Japanese Encephalitis by CD11c^hi Dendritic Cell Ablation Is Associated with an Imbalance in Regulatory Foxp3⁺ and IL-17⁺CD4⁺ Th17 Cells and in Ly-6C^hi and Ly-6C^lo Monocytes

Abstract

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 CD11chi dendritic cell (DC) ablation in CD11c-DTR transgenic mice. Moreover, CD11chi DC ablation led to abnormal differentiation of CD11b+Ly-6Chi 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-6Chi and Ly-6Clo monocytes. CD11chi 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 CD11chi DC-ablated mice. In addition, CD11chi DC-ablated mice showed higher frequency and total number of inflammatory CD11b+Ly-6Chi monocytes, whereas CD11b+Ly-6Clo monocytes were detected with lower frequency and total number in CD11chi DC-ablated mice. Furthermore, CD11chi DC ablation altered the phenotype and function of CD11b+Ly-6Clo monocytes, resulting in lower levels of activation marker and anti-inflammatory cytokine (IL-10 and TGF-β) expression. Collectively, these results indicate that CD11chi DC ablation caused an imbalance in CD4+ Th17/Treg cells and CD11b+Ly-6Chi/Ly-6Clo monocytes in the lymphoid tissue and CNS during JE progression. This imbalanced orchestration of pro- and anti-inflammatory leukocytes following CD11chi DC ablation may contribute to the exacerbation of JE.

Polymeric Nanoparticles Containing Both Antigen and Vitamin D3 Induce Antigen-Specific Immune Suppression

“…Both in vivo and in vitro experiments have demonstrated that DCs differentiated in the presence of aVD 3 exhibit the properties of tolerogenic DCs characterized by downregulated CD40, CD80, and CD86 expression, low IL-12 production, and enhanced IL-10 secretion (2,7-10). Moreover, these DCs act as poor activators of antigen-primed T cells but stimulate the generation of Tregs, which play critical roles in the antigen-specific immune suppression (10-14,34). The above findings showed that aVD 3 exerts beneficial effects on the immune function, particularly in the context of autoimmunity, via generation of tolerogenic DCs.…”

DNAJC14 Ameliorates Inner Ear Degeneration in the DFNB4 Mouse Model

“…The JEV Beijing-1 strain propagated in a mosquito cell line (C6/36) was kindly supplied by Dr. S.K. Eo (Chonbuk University, Iksan, Korea) 29 . Virus stocks (10 6 pfu/mL) were titrated using a conventional plaque assay and stored in aliquots at −80°C until use.…”

Indispensable Role of CX3CR1+ Dendritic Cells in Regulation of Virus-Induced Neuroinflammation Through Rapid Development of Antiviral Immunity in Peripheral Lymphoid Tissues

“…The CX 3 CR1 gfp/gfp (H-2 b ) mice originally obtained from Jackson laboratory (Bar Harbor, ME, USA) were generously provided by Dr. Doo Hyun Jung (Seoul National University, Seoul, Korea) and crossed with C57BL/6 mice to generate CX 3 CR1 +/gfp heterozygous mice. The JEV Beijing-1 strain was propagated in a mosquito cell line C6/36 using DMEM supplemented with 2% FBS, penicillin (100 U/ml), and streptomycin (100 U/ml) as described previously (47). The recombinant vaccinia virus expressing chicken ovalbumin (OVA) was obtained from Dr. Jonathan W. Yewdell (National Institutes of Health, Bethesda, MD, USA) and propagated in CV-1 (American Type Culture Collection, Manassas, VA, USA, CCL70) cell line (48).…”