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Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic_NatureCommunications.pdf (5.09 MB)

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2022-06-07

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cc by (c) Umeshappa, Channakeshava Sokke et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/209280

Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity

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https://doi.org/10.1038/s41467-022-30759-w

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Invariant NKT (iNKT) cells comprise a heterogeneous group of non-circulating, tissue-resident T lymphocytes that recognize glycolipids, including alpha-galactosylceramide (?GalCer), in the context of CD1d, but whether peripheral iNKT cell subsets are terminally differentiated remains unclear. Here we show that mouse and human liver-resident ?GalCer/CD1d-binding iNKTs largely correspond to a novel Zbtb16+Tbx21+Gata3+MaflowRorc- subset that exhibits profound transcriptional, phenotypic and functional plasticity. Repetitive in vivo encounters of these liver iNKT (LiNKT) cells with intravenously delivered ?GalCer/CD1d-coated nanoparticles (NP) trigger their differentiation into immunoregulatory, IL-10+IL-21-producing Zbtb16highMafhighTbx21+Gata3+Rorc- cells, termed LiNKTR1, expressing a T regulatory type 1 (TR1)-like transcriptional signature. This response is LiNKT-specific, since neither lung nor splenic tissue-resident iNKT cells from ?GalCer/CD1d-NP-treated mice produce IL-10 or IL-21. Additionally, these LiNKTR1 cells suppress autoantigen presentation, and recognize CD1d expressed on conventional B cells to induce IL-10+IL-35-producing regulatory B (Breg) cells, leading to the suppression of liver and pancreas autoimmunity. Our results thus suggest that LiNKT cells are plastic for further functional diversification, with such plasticity potentially targetable for suppressing tissue-specific inflammatory phenomena.© 2022. The Author(s).

Matèries

Malalties autoimmunitàries, Cèl·lules T

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Autoimmune diseases, T cells

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Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

UMESHAPPA, Channakeshava sokke, SOLÉ, Patricia, YAMANOUCHI, Jun, MOHAPATRA, Saswat, SUREWAARD, Bas g. j., GARNICA CAPARRÓS, Josep, SINGHA, Santiswarup, MONDAL, Debajyoti, CORTÉS VICENTE, Elena, D'MELLO, Charlotte, MASON, Andrew, KUBES, Paul, SERRA, Pau, YANG, Yang, SANTAMARIA, Pere. Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity. _Nature Communications_. 2022. Vol. 13, núm. 1. [consulta: 20 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/209280]

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