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  • Review Article
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Importance of lymphocyte–stromal cell interactions in autoimmune and inflammatory rheumatic diseases

Nature Reviews Rheumatology volume 17, pages 550–564 (2021)Cite this article

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Abstract

Interactions between lymphocytes and stromal cells have an important role in immune cell development and responses. During inflammation, stromal cells contribute to inflammation, from induction to chronicity or resolution, through direct cell interactions and through the secretion of pro-inflammatory and anti-inflammatory mediators. Stromal cells are imprinted with tissue-specific phenotypes and contribute to site-specific lymphocyte recruitment. During chronic inflammation, the modified pro-inflammatory microenvironment leads to changes in the stromal cells, which acquire a pathogenic phenotype. At the site of inflammation, infiltrating B cells and T cells interact with stromal cells. These interactions induce a plasma cell-like phenotype in B cells and T cells, associated with secretion of immunoglobulins and inflammatory cytokines, respectively. B cells and T cells also influence the stromal cells, inducing cell proliferation, molecular changes and cytokine production. This positive feedback loop contributes to disease chronicity. This Review describes the importance of these cell interactions in chronic inflammation, with a focus on human disease, using three selected autoimmune and inflammatory diseases: rheumatoid arthritis, psoriatic arthritis (and psoriasis) and systemic lupus erythematosus. Understanding the importance and disease specificity of these interactions could provide new therapeutic options.

Key points

  • During chronic inflammation, the pro-inflammatory environment leads to changes in stromal cells, and these altered phenotypes contribute to disease induction and chronicity.

  • At inflammatory sites, infiltrating B cells and T cells interact with pathogenic stromal cells, promoting inflammation that in turn induces and maintains the pathogenic phenotype of stromal cells.

  • Interactions with stromal cells induce accumulation, activation and survival of T lymphocytes and B lymphocytes, through direct cell contact and soluble factors.

  • Despite common characteristics such as the involvement of the T helper 17 axis, inflammatory diseases differ, such as in affected sites and types and phenotypes of stromal cells.

  • These differences can affect immune cell–stromal cell interactions and their resulting effects on cell activation, proliferation and cytokine production.

  • A better understanding of lymphocyte–stromal cell interactions is needed to determine how heterogeneity among these cells, including pathogenic cell subsets, could be used to stratify patients and be targeted more specifically.

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Fig. 1: Synoviocyte heterogeneity in RA.
Fig. 2: Important stromal cell–immune cell interactions during autoimmune and inflammatory diseases.
Fig. 3: Targeting of cell interactions.

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Acknowledgements

The work of the authors is supported in part by a grant from the Société Française de Rhumatologie.

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  1. Immunogenomics and Inflammation Research Unit, University of Lyon, Department of Immunology and Rheumatology, Hospital Edouard Herriot, Lyon, France

    Mélissa Noack & Pierre Miossec

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Noack, M., Miossec, P. Importance of lymphocyte–stromal cell interactions in autoimmune and inflammatory rheumatic diseases. Nat Rev Rheumatol 17, 550–564 (2021). https://doi.org/10.1038/s41584-021-00665-4

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