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BCL6 is required for the thymic development of TCRαβ+CD8αα+ intraepithelial lymphocyte lineage.
- Source :
- Science Immunology; 2024, Vol. 9 Issue 92, p1-16, 16p
- Publication Year :
- 2024
-
Abstract
- TCRαβ<superscript>+</superscript>CD8αα<superscript>+</superscript> intraepithelial lymphocytes (CD8αα<superscript>+</superscript> αβ IELs) are a specialized subset of T cells in the gut epithelium that develop from thymic agonist selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in the near absence of CD8αα<superscript>+</superscript> αβ IELs. BCL6 was expressed by approximately 50% of CD8αα<superscript>+</superscript> αβ IELs and by the majority of thymic PD1<superscript>+</superscript> IELps after agonist selection. Bcl6 deficiency blocked early IELp generation in the thymus, and its expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4<superscript>+</superscript>CD8<superscript>+</superscript> double-positive thymocytes exhibited increased apoptosis during agonist selection and impaired IELp differentiation and maturation. Together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα<superscript>+</superscript> αβ IELs. Editor's summary: Intraepithelial lymphocytes (IELs) reside within the intestinal epithelium, where they regulate immune tolerance. Unconventional CD8αα<superscript>+</superscript> αβ IELs are selected from thymic IEL precursors (IELps) after strong TCR signaling; however, the transcription factors governing this process of agonist selection are not well defined. Xing et al. found that mice lacking the transcription factor BCL6 in αβ T cells almost did not develop CD8αα<superscript>+</superscript> αβ IELs. Thymic IELps up-regulated BCL6 after TCR stimulation, and BCL6 expression was required for their survival, differentiation, and maturation. These findings identify that BCL6 is required for the development of unconventional CD8αα<superscript>+</superscript> αβ IELs during agonist selection. —Hannah Isles [ABSTRACT FROM AUTHOR]
- Subjects :
- LYMPHOCYTES
T cells
INTESTINAL mucosa
TRANSCRIPTION factors
THYMOCYTES
Subjects
Details
- Language :
- English
- ISSN :
- 24709468
- Volume :
- 9
- Issue :
- 92
- Database :
- Complementary Index
- Journal :
- Science Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 175795045
- Full Text :
- https://doi.org/10.1126/sciimmunol.adk4348