Dataset Information

Development of Fit Epidermal Resident Memory T Cells Requires Antigen Encounter in the Skin

ABSTRACT: CD8+ tissue resident memory T cells (TRM) develop from effectors that are recruited into peripheral tissues by infection or inflammation where they persist and provide defense against subsequent challenges. Long-term persistence of epidermal TRM requires autocrine TGFβ that is transactivated by integrins expressed on keratinocytes. In response to inflammation, the availability of TGFβ transactivation is limited. Antigen-experienced TRM that encountered antigen in the epidermis during their development are more fit and outcompete bystander TRM for TGFβ transactivation resulting in their enrichment in the epidermis. Transcriptomic analysis of endogenous epidermal TRM revealed that antigen-experienced TRM were enriched for TRM signature genes while bystander TRM retained the transcriptome of an earlier developmental state. Following antigen recall, antigen-experienced TRM displayed accelerated proliferation kinetics compared with bystanders that was determined by the TCR signal-strength during their differentiation the skin. Finally, antigen experienced TRM expressed TGFβRIII, which increases avidity of the TGFβRI/II receptor complex. Selective ablation of Tgfbr3 from antigen experienced TRM reduced their capacity to persist when TGFβ activation was limited thus rendering them phenotypically like bystander TRM. In sum, antigen-driven TCR signaling in the epidermis during TRM differentiation represents a required final step in ontogeny resulting in a lowered requirement on TGFβ transactivation for persistence and increased proliferation during recall responses that together result in the enhanced fitness of antigen-experience epidermal TRM.

ORGANISM(S): Mus musculus

PROVIDER: GSE283941 | GEO | 2024/12/10

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Cell fates are defined by specific transcriptional program. Previously, we developed a unique stem cell regeneration mouse model, in which transcriptional program for ectoderm organs such as tooth and skin is switched. Genomic deletion of one subunit of Mediator complex, Med1, resulted in defective enamel regeneration, in which dental stem cells were inhibited from undergoing transcriptional program for dental fate. In stead, they exerted skin program for both hair and epidermis, and post-natally regenerate ectopic hairs in the incisors. Here, we report that Med1 also modulates epidermal and hair cell fates in the skin. Med1 ablation further enhanced epidermal and sebocyte fates, and accelerated injury induced epidermal regeneration. However, it blunted hair fate resulting in hair loss in the skin. Ablation of Med1 increased the number of isthmus stem cells and epidermal stem cells, which regenerate epidermis during cutaneous wound healing process. Med1 deficiency also constitutively activated these stem cells and increased their proliferation. Microarray profiling indicated that Med1 deletion causes activation of β-catenin and suppression of TGFβ signaling. Med1 deficiency induced the expression of β-catenin target genes to control cell fate and proliferation. It also decreased TGFβ expression in interfollicular epidermis. Med1 deficiency increased the proliferation and migration of epidermal cells, and induced nuclear translocation of β-catenin, and decreased TGFβ1 expression in vitro. Our finding together with previous observations demonstrated that Med1 governs ectoderm cell fate in both tooth and skin. Med1 ablation blunts hair fate but induces epidermal and sebocyte cell fates to accelerated injury induced epidermal regeneration in the skin. Accelerated regeneration is derived from constitutive activation of epidermal stem cells accompanied with increased proliferation and migration of their progeny by balancing of β-catenin induced growth promoting and TGFβ mediated growth inhibitory activities in the skin.

Dataset Information

Development of Fit Epidermal Resident Memory T Cells Requires Antigen Encounter in the Skin

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets