Fibroblastic reticular cell response to dendritic cells requires coordinated activity of podoplanin, CD44 and CD9.

Autor:	de Winde CM; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Makris S; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Millward LJ; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Cantoral-Rebordinos JA; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Benjamin AC; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Martínez VG; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Acton SE; Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2021 Jul 15; Vol. 134 (14). Date of Electronic Publication: 2021 Jul 22.
DOI:	10.1242/jcs.258610
Abstrakt:	In adaptive immunity, CLEC-2+ dendritic cells (DCs) contact fibroblastic reticular cells (FRCs) inhibiting podoplanin-dependent actomyosin contractility, permitting FRC spreading and lymph node expansion. The molecular mechanisms controlling lymph node remodelling are incompletely understood. We asked how podoplanin is regulated on FRCs in the early phase of lymph node expansion, and which other proteins are required for the FRC response to DCs. We find that podoplanin and its partner proteins CD44 and CD9 are differentially expressed by specific lymph node stromal populations in vivo, and their expression in FRCs is coregulated by CLEC-2 (encoded by CLEC1B). Both CD44 and CD9 suppress podoplanin-dependent contractility. We find that beyond contractility, podoplanin is required for FRC polarity and alignment. Independently of podoplanin, CD44 and CD9 affect FRC-FRC interactions. Furthermore, our data show that remodelling of the FRC cytoskeleton in response to DCs is a two-step process requiring podoplanin partner proteins CD44 and CD9. Firstly, CLEC-2 and podoplanin binding inhibits FRC contractility, and, secondly, FRCs form protrusions and spread, which requires both CD44 and CD9. Together, we show a multi-faceted FRC response to DCs, which requires CD44 and CD9 in addition to podoplanin. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2021. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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