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Hnf4 controls gut and liver gene programs in the thymus [scRNAseq]

ABSTRACT: We profiled medullary thymic epithelial cells by scRNA-seq to investigate mechanisms of T-cell tolerance.

ORGANISM(S): Mus musculus

PROVIDER: GSE225660 | GEO | 2023/06/26

REPOSITORIES: GEO

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Hnf4 controls gut and liver gene programs in the thymus [bulk_RNAseq]

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Hnf4 controls gut and liver gene programs in the thymus

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Hnf4 controls gut and liver gene programs in the thymus [scRNAseq]

Project description:Hnf4 controls gut and liver gene programs in the thymus [scRNAseq]

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Comparison of RelB-/- and RelB+/- thymi

Project description:Thymic medullary epithelial cell (mTEC) expression of the autoimmune regulator AIRE, and of tissue-specific antigens, is controlled by members of the non-canonical NF-kB signalling pathway, including RelB and NF-kB2. Of the genes in this pathway, RelB-/- mice develop a particularly severe multi-organ autoimmune syndrome, resembling Foxp3-deficiency. RelB-/- mice have medullary atrophy and few mTECs but the mechanism is unknown. We show that RelB is required for expression of medullary chemokines and mTEC AIRE, selection of a diverse peripheral T cell repertoire, and for peripheral Foxp3+ Treg function. VÎ² families of T cells infiltrating diseased peripheral organs and thymic Treg were similarly skewed. Surprisingly, medullary atrophy results from intra-thymic granulocyte infiltration, consequent upon the Th2-mediated autoimmune disease. Dominant tolerance corrects thymic inflammatory disease and loss of thymic function. We demonstrate a reversible RelB-dependent inflammatory mechanism for loss of central tolerance associated with medullary atrophy. Thymi from 4 RelB+/- mice and 3 RelB-/- mice were profiled by microarays

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Hnf4 controls gut and liver gene programs in the thymus

Project description:Hnf4 controls gut and liver gene programs in the thymus

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Single cell RNA sequencing of thymic dendritic cells reveals molecular determinants of antigen transfer in the thymus

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