TREM-2 mediates dendritic cell–induced NO to suppress Th17 activation and ameliorate chronic kidney diseases

Ching Cheng Lin, Ti Yung Chang, Yong Chen Lu, Yun Syuan Wu, Wei Huang, Wei Chi Lo, Guan Fu Liu, Wei Chan Hsu, Pamela S. Ohashi, Tak W. Mak, Jong Ling Fuh, Hui Chen Chen, Der-Cherng Tarng, Nien Jung Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract: Chronic kidney disease (CKD) is a global public health issue. CKD is caused by the infiltration of various myeloid cell types into renal tissue, resulting in renal fibrosis and tubular atrophy. Unilateral ureteral obstruction (UUO) surgery in mice is a model of CKD and characterized by high expression of the anti-inflammatory receptor, Triggering receptor expressed on myeloid cells 2 (TREM-2), on myeloid cells in affected kidneys. Here, we show that iNOS expression and nitric oxide (NO) induction were decreased in Trem-2−/− bone marrow-derived DCs (BMDCs) and in Trem-2 knockdown DC2.4 cells stimulated in vitro with LPS. The nitration of RORγt was decreased in T cells co-cultured with LPS-stimulated Trem-2−/− BMDCs, enhancing IL-17 production. UUO-treated Trem-2−/− mice displayed aggravated renal pathogenesis accompanied by greater neutrophil infiltration and enhanced Th17 cells differentiation, phenotypes that could be rescued by the administration of L-arginine (a biological precursor of NO). Our data identify a key mechanism underlying TREM-2-mediated NO to modulate the cellular crosstalk between dendritic cells, Th17, and neutrophils. Furthermore, we also reveal TREM-2 as a potential novel target for the development of anti-inflammatory drugs in CKD treatment. Key messages: The expression of TREM-2 is increased in nephritisTREM-2+ DCs maintain NO production to negatively regulate Th17 differentiationThe severe pathologies of nephritis can be rescued by L-arginine supplementation Graphical Abstract: [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)917-931
Number of pages15
JournalJournal of Molecular Medicine
Volume100
Issue number6
DOIs
StatePublished - Jun 2022

Keywords

  • Dendritic cells
  • Nitric oxide
  • Th17
  • TREM-2
  • UUO

Fingerprint

Dive into the research topics of 'TREM-2 mediates dendritic cell–induced NO to suppress Th17 activation and ameliorate chronic kidney diseases'. Together they form a unique fingerprint.

Cite this