Toll‐like receptors control the accumulation of neutrophils in lymph nodes that expand CD4 + T cells during experimental autoimmune encephalomyelitis - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles European Journal of Immunology Year : 2023

Toll‐like receptors control the accumulation of neutrophils in lymph nodes that expand CD4 + T cells during experimental autoimmune encephalomyelitis

Abstract

Toll-like receptors (TLR) control the activation of dendritic cells that prime CD4(+) 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(+) 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(+) T cell expansion. Addressing the underpinning mechanisms revealed that CD4(+) 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(+) T cell expansion in lymph nodes, and the counter-regulatory role of TLR signaling in this process.

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Immunology
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hal-04023000 , version 1 (10-03-2023)

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Ping Shen, Madlen Rother, Ulrik Stervbo, Vicky Lampropoulou, Elisabeth Calderon-Gomez, et al.. Toll‐like receptors control the accumulation of neutrophils in lymph nodes that expand CD4 + T cells during experimental autoimmune encephalomyelitis. European Journal of Immunology, 2023, 53 (2), pp.2250059. ⟨10.1002/eji.202250059⟩. ⟨hal-04023000⟩
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