Immunofibroblasts regulate LTα3 expression in tertiary lymphoid structures in a pathway dependent on ICOS/ICOSL interaction.
Author
Nayar, SabaPontarini, Elena
Campos, Joana
Berardicurti, Onorina
Smith, Charlotte G
Asam, Saba
Gardner, David H
Colafrancesco, Serena
Lucchesi, Davide
Coleby, Rachel
Chung, Ming-May
Iannizzotto, Valentina
Hunter, Kelly
Bowman, Simon J
Carlesso, Gianluca
Herbst, Ronald
McGettrick, Helen M
Browning, Jeff
Buckley, Christopher D
Fisher, Benjamin A
Bombardieri, Michele
Barone, Francesca
Publication date
2022-05-04
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Show full item recordAbstract
mmunofibroblasts have been described within tertiary lymphoid structures (TLS) that regulate lymphocyte aggregation at sites of chronic inflammation. Here we report, for the first time, an immunoregulatory property of this population, dependent on inducible T-cell co-stimulator ligand and its ligand (ICOS/ICOS-L). During inflammation, immunofibroblasts, alongside other antigen presenting cells, like dendritic cells (DCs), upregulate ICOSL, binding incoming ICOS + T cells and inducing LTα3 production that, in turn, drives the chemokine production required for TLS assembly via TNFRI/II engagement. Pharmacological or genetic blocking of ICOS/ICOS-L interaction results in defective LTα expression, abrogating both lymphoid chemokine production and TLS formation. These data provide evidence of a previously unknown function for ICOSL-ICOS interaction, unveil a novel immunomodulatory function for immunofibroblasts, and reveal a key regulatory function of LTα3, both as biomarker of TLS establishment and as first driver of TLS formation and maintenance in mice and humans.Citation
Nayar S, Pontarini E, Campos J, Berardicurti O, Smith CG, Asam S, Gardner DH, Colafrancesco S, Lucchesi D, Coleby R, Chung MM, Iannizzotto V, Hunter K, Bowman SJ, Carlesso G, Herbst R, McGettrick HM, Browning J, Buckley CD, Fisher BA, Bombardieri M, Barone F. Immunofibroblasts regulate LTα3 expression in tertiary lymphoid structures in a pathway dependent on ICOS/ICOSL interaction. Commun Biol. 2022 May 4;5(1):413. doi: 10.1038/s42003-022-03344-6Type
ArticleAdditional Links
http://www.nature.com/commsbio/PMID
35508704Journal
Communications BiologyPublisher
Nature Publishing Groupae974a485f413a2113503eed53cd6c53
10.1038/s42003-022-03344-6