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

doi:10.1111/sji.13214

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

Journal article

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Peer reviewed

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 and Naresh Sachdeva

Scandinavian journal of immunology, v 96(5), pn/a

Nov 2022

DOI: https://doi.org/10.1111/sji.13214

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Abstract

CD4+ T cells

effector T cells

immune suppression

oligodeoxynucleotides

T cell proliferation

TLR9

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.

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Details

Title: TLR9 signalling activation via direct ligation and its functional consequences in CD4 + T cells
Creators: Ravi Kumar Sharma - Post Graduate Institute of Medical Education and Research
Jyoti Sharma - Post Graduate Institute of Medical Education and Research
Rajendra Kumar - Indian Institute of Science Education and Research Mohali
Darshan Badal - Post Graduate Institute of Medical Education and Research
Ajinkya Pattekar - Drexel University
Shobha Sehgal - Post Graduate Institute of Medical Education and Research
Amod Gupta - Post Graduate Institute of Medical Education and Research
Pooja Jain - Drexel University
Naresh Sachdeva - Post Graduate Institute of Medical Education and Research
Publication Details: Scandinavian journal of immunology, v 96(5), pn/a
Publisher: Wiley
Number of pages: 18
Grant note: Department of Biotechnology, Ministry of Science and Technology (BT/01/CEIB/11/02) Fogarty International Center (D43 TW009588) National Institutes of Health (1R01NS097147) Indian Council of Medical Research (3/1/3/JRF‐2012/HRD‐87)
Resource Type: Journal article
Language: English
Academic Unit: Microbiology and Immunology
Web of Science ID: WOS:000852592400001
Scopus ID: 2-s2.0-85137768048
Other Identifier: 991020545409904721

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Collaboration types: Domestic collaboration; International collaboration
Web of Science research areas: Immunology