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

Autor: Shen P; Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, Germany.; Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.; Stem Cell and Biotherapy Engineering Research Center of Henan Province, College of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, 453003, China., Rother M; Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, Germany., Stervbo U; Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, Germany., Lampropoulou V; Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, Germany.; Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Calderon-Gomez E; Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, Germany., Roch T; Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, Germany., Hilgenberg E; Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, Germany., Ries S; Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, Germany., Kühl AA; Institute of Pathology/RCIS, Charité, Campus Benjamin Franklin, 12203, Berlin, Germany., Jouneau L; Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, 78350, France., Boudinot P; Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, 78350, France., Fillatreau S; Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, Germany.; Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, Paris, F-75015, France.; Service Immunologie Biologique, AP-HP, Hôpital Necker-Enfants Malades, Paris, F-75015, France.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2023 Feb; Vol. 53 (2), pp. e2250059. Date of Electronic Publication: 2022 Dec 13.
DOI: 10.1002/eji.202250059
Abstrakt: 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.
(© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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