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  • Review Article
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Splenic stromal niches in homeostasis and immunity

Nature Reviews Immunology volume 23, pages 705–719 (2023)Cite this article

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Abstract

The spleen is a gatekeeper of systemic immunity where immune responses against blood-borne pathogens are initiated and sustained. Non-haematopoietic stromal cells construct microanatomical niches in the spleen that make diverse contributions to physiological spleen functions and regulate the homeostasis of immune cells. Additional signals from spleen autonomic nerves also modify immune responses. Recent insight into the diversity of the splenic fibroblastic stromal cells has revised our understanding of how these cells help to orchestrate splenic responses to infection and contribute to immune responses. In this Review, we examine our current understanding of how stromal niches and neuroimmune circuits direct the immunological functions of the spleen, with a focus on T cell immunity.

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Fig. 1: Spleen architecture and the white pulp niche in mice and humans.
Fig. 2: Spleen fibroblastic cell niches.
Fig. 3: Spleen remodelling and control of T cell fate during infection.

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Acknowledgements

The authors thank J. Groom, H. Horsnell and A. Haque for critical input. S.N.M. is a recipient of a National Health and Medical Research Council (NHMRC) Senior Research Fellowship.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia

    Yannick O. Alexandre & Scott N. Mueller

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The authors contributed equally to all aspects of the article.

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Glossary

Conventional type 1 DCs

(cDC1s). Dendritic cells (DCs) that are specialized in the uptake and cross-presentation of exogenous antigens for T cell activation. cDC1s dominate CD8+ T cell priming in many diseases.

Conventional type 2 DCs

(cDC2s). Dendritic cells (DCs) that are specialized for the priming of CD4+ T cell responses and T helper cell differentiation.

Fibroblastic reticular cells

(FRCs). Specialized fibroblasts found in lymphoid organs that construct and support microenvironments for immune cells.

Marginal zone

(MZ). Region of the spleen that separates the red pulp from the white pulp. The MZ is a transit area for immune cells that arrive from the blood circulation into the spleen. The main role of the MZ is to filter antigens from the blood circulation.

Memory precursor effector T cells

Effector T cells that are present during immune responses that display an enhanced ability to form memory T cells and persist in the body.

Progenitor exhausted T cells

These cells retain stem-like cell properties during chronic infections and cancer with the capacity to expand and differentiate into exhausted T cells.

Red pulp

(RP). Compartment of the spleen filled with venous sinuses and where red blood cells are filtered.

Short-lived effector T cells

The majority of the effector T cells induced during immune responses are short-lived and die via apoptosis after the resolution of an infection.

Trabeculae

Connective tissue that protrudes from the capsule into the splenic tissue and contains blood vessels and associated nerves. The trabeculae and capsule provide structure and rigidity to the spleen.

White pulp

(WP). Lymphoid tissue component of the spleen devoid of red blood cells and where adaptative immune responses are initiated. The WP surrounds the central arteries.

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Alexandre, Y.O., Mueller, S.N. Splenic stromal niches in homeostasis and immunity. Nat Rev Immunol 23, 705–719 (2023). https://doi.org/10.1038/s41577-023-00857-x

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