Amazing stuff!
"... In a new study ... researchers reveal how cells known as tissue-resident memory CD8 T cells, play unique and specialized roles based on where they are located within the small intestine. Tissue-resident memory cells provide a local first line of defense against re-infection and call for “backup” from other immune cells and are also critical for maintaining peace in a tissue exposed to many outside pathogens.
This discovery sheds light on how tissue-resident memory CD8 T cells adapt to their location in the body, ensuring a coordinated and effective immune response and how microenvironments and cellular interactions shape this location-specific adaptation. ..."
From the abstract:
"Tissue-resident memory CD8 T (TRM) cells provide protection from infection at barrier sites. In the small intestine, TRM cells are found in at least two distinct subpopulations:
one with higher expression of effector molecules and
another with greater memory potential.
However, the origins of this diversity remain unknown.
Here we proposed that distinct tissue niches drive the phenotypic heterogeneity of TRM cells.
To test this, we leveraged spatial transcriptomics of human samples, a mouse model of acute systemic viral infection and a newly established strategy for pooled optically encoded gene perturbations to profile the locations, interactions and transcriptomes of pathogen-specific TRM cell differentiation at single-transcript resolution.
We developed computational approaches to capture cellular locations along three anatomical axes of the small intestine and to visualize the spatiotemporal distribution of cell types and gene expression.
Our study reveals that the regionalized signalling of the intestinal architecture supports two distinct TRM cell states:
differentiated TRM cells and progenitor-like TRM cells, located in the upper villus and lower villus, respectively.
This diversity is mediated by distinct ligand–receptor activities, cytokine gradients and specialized cellular contacts. Blocking TGFβ or CXCL9 and CXCL10 sensing by antigen-specific CD8 T cells revealed a model consistent with anatomically delineated, early fate specification. Ultimately, our framework for the study of tissue immune networks reveals that T cell location and functional state are fundamentally intertwined."
Fig. 1: Characterization of the spatial and transcriptional state of antigen-specific CD8 T cells in response to acute viral infection in the mouse SI with spatial transcriptomics.
Fig. 2: Intestinal regionalization along key axes informs TRM cell diversity in the mouse intestine.
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