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The transcription factor BCL-6 controls early development of innate-like T cells
BSRC Alexander Fleming, Greece.
BSRC Alexander Fleming, Greece; Univ Thessaly, Greece.
BSRC Alexander Fleming, Greece.
BSRC Alexander Fleming, Greece.
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2020 (English)In: Nature Immunology, ISSN 1529-2908, E-ISSN 1529-2916, Vol. 21, p. 1058-1069Article in journal (Refereed) Published
Abstract [en]

Verykokakis and colleagues show that the transcription factor BCL-6 is highly expressed in stage 0 NKT and is absolutely required for innate T cell lineage development. BCL-6 acts to modify the chromatin landscape and is needed to promote the ST0-ST1 transition and PLZF expression. Innate T cells, including invariant natural killer T (iNKT) and mucosal-associated innate T (MAIT) cells, are a heterogeneous T lymphocyte population with effector properties preprogrammed during their thymic differentiation. How this program is initiated is currently unclear. Here, we show that the transcription factor BCL-6 was transiently expressed in iNKT cells upon exit from positive selection and was required for their proper development beyond stage 0. Notably, development of MAIT cells was also impaired in the absence ofBcl6. BCL-6-deficient iNKT cells had reduced expression of genes that were associated with the innate T cell lineage, includingZbtb16, which encodes PLZF, and PLZF-targeted genes. BCL-6 contributed to a chromatin accessibility landscape that was permissive for the expression of development-related genes and inhibitory for genes associated with naive T cell programs. Our results revealed new functions for BCL-6 and illuminated how this transcription factor controls early iNKT cell development.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2020. Vol. 21, p. 1058-1069
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-168545DOI: 10.1038/s41590-020-0737-yISI: 000553242700003PubMedID: 32719520OAI: oai:DiVA.org:liu-168545DiVA, id: diva2:1462162
Note

Funding Agencies|European Commission H2020-MSCA-IF grant [655271]; Hellenic Foundation for Research and Innovation grant [486]; National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R56 AI104303, R01 AI123396]; Stavros Niarchos Foundation [GRA-14451]; Knut and Alice Wallenbergs FoundationKnut & Alice Wallenberg Foundation; CancerfondenSwedish Cancer Society; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [5R01 AI32771]; Operational Programme "Competitiveness, Entrepreneurship and Innovation" (NSRF) [MIS 5002562]; European UnionEuropean Union (EU)

Available from: 2020-08-28 Created: 2020-08-28 Last updated: 2021-04-12

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