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Toll-like receptors control the accumulation of neutrophils in lymph nodes that expand CD4 + T cells during experimental autoimmune encephalomyelitis.
- Source :
-
European journal of immunology [Eur J Immunol] 2023 Feb; Vol. 53 (2), pp. e2250059. Date of Electronic Publication: 2022 Dec 13. - Publication Year :
- 2023
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Abstract
- Toll-like receptors (TLR) control the activation of dendritic cells that prime CD4 <superscript>+</superscript> T cells in draining lymph nodes, where these T cells then undergo massive clonal expansion. The mechanisms controlling this clonal T cell expansion are poorly defined. Using the CD4 <superscript>+</superscript> T cell-mediated disease experimental autoimmune encephalomyelitis (EAE), we show here that this process is markedly suppressed when TLR9 signaling is increased, without noticeably affecting the transcriptome of primed T cells, indicating a purely quantitative effect on CD4 <superscript>+</superscript> T cell expansion. Addressing the underpinning mechanisms revealed that CD4 <superscript>+</superscript> T cell expansion was preceded and depended on the accumulation of neutrophils in lymph nodes a few days after immunization. Underlying the importance of this immune regulation pathway, blocking neutrophil accumulation in lymph nodes by treating mice with a TLR9 agonist inhibited EAE progression in mice with defects in regulatory T cells or regulatory B cells, which otherwise developed a severe chronic disease. Collectively, this study demonstrates the key role of neutrophils in the quantitative regulation of antigen-specific CD4 <superscript>+</superscript> T cell expansion in lymph nodes, and the counter-regulatory role of TLR signaling in this process.<br /> (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 1521-4141
- Volume :
- 53
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 36458588
- Full Text :
- https://doi.org/10.1002/eji.202250059