TLR9 signalling activation via direct ligation and its functional consequences in CD4 + T cells

Ravi Kumar Sharma, Jyoti Sharma, Rajendra Kumar, Darshan Badal, Ajinkya Pattekar, Shobha Sehgal, Amod Gupta, Pooja Jain, Naresh Sachdeva

Research output: Contribution to journalArticlepeer-review

Abstract

CpG Oligodeoxynucleotides (ODNs) are established TLR9 ligands; however, their functional responses in CD4+ T cells are believed to be independent of TLR9 and MyD88. We studied ligand-receptor interactions of ODN 2216 and TLR9 in human CD4+ T cells and assessed their consequences in terms of TLR9 signalling and cell phenotype. We demonstrated that the uptake of ODN 2216, a synthetic TLR9 agonist, is controlled by TLR9 signalling molecules and results in an increase in the expression of TLR9 signalling molecules, regulated via a feedback mechanism. Next, the uptake of ODN 2216 resulted in TLR9 signalling dependent but MyD88 independent increase in expression of TGF-β. Finally, ODN 2216 treated CD4+ T cells showed an anti-inflammatory phenotype that was similar to Th3 type of regulatory T cells. These Th3-like cells were able to suppress the proliferation of untreated CD4+ T cells. Collectively, our results demonstrate a direct and interdependent relationship between ODN 2216 uptake and TLR9 signalling in CD4+ T cells. Our findings thus pave the way for future research to explore direct modulation of adaptive immune cells, using innate immune ligands, to subvert exaggerated inflammatory responses.

Original languageEnglish (US)
Article numbere13214
JournalScandinavian Journal of Immunology
Volume96
Issue number5
DOIs
StatePublished - Nov 2022

Keywords

  • CD4+ T cells
  • T cell proliferation
  • TLR9
  • effector T cells
  • immune suppression
  • oligodeoxynucleotides

ASJC Scopus subject areas

  • Immunology

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