AUTHOR=Li Lanjiao , Chen Jichun , Wang Zhenyan , Xu Yan , Yao Hao , Lei Wulong , Zhou Xiyuan , Zheng Minming 

TITLE=NECA alleviates inflammatory responses in diabetic retinopathy through dendritic cell toll-like receptor signaling pathway

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1415004

DOI=10.3389/fimmu.2024.1415004

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>This study examined the impact of 5’-(N- ethylcarboxamido)adenosine (NECA) in the peripheral blood of healthy individuals, those with diabetes mellitus, diabetic retinopathy (DR), and C57BL/6 mice, both <italic>in vivo</italic> and <italic>in vitro</italic>.</p></sec><sec><title>Methods</title><p>Enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FCM) were used to evaluate the effects of NECA on dendritic cells (DCs) and mouse bone marrow-derived dendritic cells (BMDCs) and the effects of NECA-treated DCs on Treg and Th17 cells. The effect of NECA on the Toll-like receptor (TLR) pathway in DCs was evaluated using polymerase chain reaction (PCR) and western blotting (WB).</p></sec><sec><title>Results</title><p>FCM and ELISA showed that NECA inhibited the expression of surface markers of DCs and BMDCs, increased anti-inflammatory cytokines and decreased proinflammatory cytokines. PCR and WB showed that NCEA decreased mRNA transcription and protein expression in the TLR-4-MyD88-NF-kβ pathway in DCs and BMDCs. The DR severity in streptozocin (STZ) induced diabetic mice was alleviated. NECA-treated DCs and BMDCs were co-cultivated with CD4+T cells, resulting in modulation of Treg and Th17 differentiation, along with cytokine secretion alterations.</p></sec><sec><title>Conclusion</title><p>NECA could impair DCs’ ability to present antigens and mitigate the inflammatory response, thereby alleviating the severity of DR.</p></sec>