Focus on Inflammatory Disease

The emerging role of resident memory T cells in protective immunity and inflammatory disease

Journal name:
Nature Medicine
Volume:
21,
Pages:
688–697
Year published:
DOI:
doi:10.1038/nm.3883
Received
Accepted
Published online

Abstract

Over the past decade, it has become clear that there is an important subset of memory T cells that resides in tissues—tissue-resident memory T (TRM) cells. There is an emerging understanding that TRM cells have a role in human tissue-specific immune and inflammatory diseases. Furthermore, the nature of the molecular signals that maintain TRM cells in tissues is the subject of much investigation. In addition, whereas it is logical for TRM cells to be located in barrier tissues at interfaces with the environment, these cells have also been found in brain, kidney, joint and other non-barrier tissues in humans and mice. Given the biology and behavior of these cells, it is likely that they have a role in chronic relapsing and remitting diseases of both barrier and non-barrier tissues. In this Review we discuss recent insights into the biology of TRM cells with a particular focus on their roles in disease, both proven and putative.

At a glance

Figures

  1. The generation of tissue TRM cells after infection of barrier tissues.
    Figure 1: The generation of tissue TRM cells after infection of barrier tissues.

    (a) Upon first encounter with a pathogen in a barrier tissue, dendritic cells carry antigen to draining lymph nodes and present it to naive T cells. Depending on the anatomic location of the lymph node, various trafficking molecules (indicated adjacent to vessels) are expressed on the expanding activated T cell population, and effector T cells with specific tissue-homing properties preferentially exit blood in peripheral tissues. Gut-draining lymph nodes induce the expression of gut-homing molecules on antigen-activated T cells, and skin-draining lymph nodes induce the expression of skin-homing molecules on antigen-activated T cells. Analogous processes, albeit less well characterized, occur in lymph nodes draining lung and reproductive mucosa. VLA-1, very late antigen 1 (α1β1 integrin). (b) Long after the pathogen has been eliminated from the barrier tissue and inflammation has resolved, populations of TRM cells remain behind in the tissue. These TRM cells retain the tissue-homing molecules originally imprinted on them and acquire a molecular program that contributes to the maintenance of these cells in peripheral tissue. In parallel, circulating memory T cells are generated, and these have the capacity to enter lymph node and recirculate into blood and tissue. Recent evidence suggests that the same naive T cell may give rise to both TRM cells and TCM cells or circulating T cells38. Adapted with permission from ref. 113, Nature Publishing Group.

  2. The role of TRM cells in tissue-specific autoimmune and inflammatory disease.
    Figure 2: The role of TRM cells in tissue-specific autoimmune and inflammatory disease.

    Right, diseases of lung, gut and skin clearly or potentially mediated by pathologically activated TRM cells. Left, diseases of normally sterile non-barrier tissues mediated by infiltrating T cells that have acquired the properties of TRM cells. Disease states in normal font indicate that there is experimental evidence supporting TRM cell causation, whereas disease states in italic font are speculation on the part of the authors. GVHD, graft-versus-host disease.

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  1. Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Chang Ook Park &
    • Thomas S Kupper

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T.S.K. is an inventor on US Patent 8691502, assigned to TremRx, Inc.

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