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Stromal–immune cell interactions

Immune cells journey throughout the body surveilling for signs of danger or damage. As they do, they are instructed by stationary tissue-resident stromal cells in their development, survival and function. Here, we present a Collection of research articles and reviews that discuss the players and factors involved in stromal–immune cell interactions in both health and disease. Understanding the cellular interactions and their mediators can help to identify potential therapeutic targets to promote immunity as well as to alleviate disease conditions. We gratefully acknowledge the generous support from Boehringer Ingelheim in sponsoring this Collection.

This Collection is editorially independent, produced with financial support from a third party. About this content.


Recent single-cell studies have revealed a previously unappreciated heterogeneity among endothelial cells that line the lymphatic sinuses of the lymph nodes. In this Review, the authors describe these various lymphatic endothelial cell types and how they support the trafficking of cells and antigens through lymph nodes.

Review Article | | Nature Reviews Immunology

Structural cells implement a broad range of immune-regulatory functions beyond their roles as barriers and connective tissues, and they utilize an epigenetically encoded potential for immune gene activation in their rapid response to viral infection.

Article | | Nature

Organoid technology has emerged as a powerful tool to maintain epithelial cells in a near-native state that can be used to better understand the interactions between epithelial cells and the immune system in tissue development, homeostasis, infection and cancer.

Review Article | | Nature Reviews Immunology

Peyer’s patches (PPs) are sites of antibody production in the gut mucosa. Carroll and colleagues show the mechanosensory channel protein Piezo1 is required for the homeostatic maintenance of PPs. Specific loss of Piezo1 in FRCs disrupt PP structure and function, resulting in reduction of fecal IgA production and gut immunity.

Article | | Nature Immunology

Further reading

Visceral adipose tissue contains populations of regulatory T cells that exhibit sexual dimorphism, determined by the surrounding niche, and differ between male and female mice in terms of cell number, phenotype, transcriptional landscape and chromatin accessibility.

Article | | Nature

Recent studies using single-cell genomic technologies and in vivo fate mapping have shown that thymic epithelial cells are far more heterogeneous than previously thought, comprising multiple subpopulations with distinct molecular and functional characteristics.

Review Article | | Nature Reviews Immunology

Ageing of the haematopoietic system is accompanied by declining erythropoiesis and lymphopoiesis. Here the authors uncover upregulated IL-6 and TGFβ signalling in aged bone marrow stroma; inhibition of these signals reverses age-related haematopoietic defects, re-balancing haematopoietic stem cell lineage output.

Article | Open Access | | Nature Communications

Thymus is a unique environment hosting the development of many T cell subsets with distinct functions. Here the authors show that medullary thymic epithelial cells (mTEC) are functionally diverse, with LTβR signaling serving differential regulation of mTEC for specific control of multiple lineages of invariant natural killer T cells.

Article | Open Access | | Nature Communications

Fibroblast-like synoviocytes in rheumatoid arthritis have an aggressive phenotype caused, in part, by epigenetic imprinting, which contributes to various pathological processes. Understanding the mechanisms underlying the cell abnormalities and phenotypes, including their spatial and temporal differences, could lead to new therapies.

Review Article | | Nature Reviews Rheumatology

The transcriptional landscape of cell populations of the mouse bone marrow microenvironment, mapped at single-cell resolution, reveals cellular heterogeneity in this niche as well as substantial transcriptional remodelling under stress conditions.

Article | | Nature

In addition to cancer cell-intrinsic effects, tumour growth can be regulated by cellular and molecular cues from the local tissue environment. This Review discusses how differences in cellular components and composition between tissue sites may influence the antitumour immune response, with potential implications for the design of therapeutic strategies.

Review Article | | Nature Reviews Cancer

Tuft cells captured the attention of immunologists with recent discoveries linking them to type 2 immunity in the small intestine. As described here, these rare secretory epithelial cells act as chemosensory sentinels that detect and relay responses through immune and neuronal cells.

Review Article | | Nature Reviews Immunology