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

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      Nature Medicine
      Springer Science and Business Media LLC

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          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.

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          Most cited references73

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          Skin immune sentinels in health and disease.

          Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.
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            Memory T cell subsets, migration patterns, and tissue residence.

            Tissues such as the skin and mucosae are frequently exposed to microbial pathogens. Infectious agents must be quickly and efficiently controlled by our immune system, but the low frequency of naive T cells specific for any one pathogen means dependence on primary responses initiated in draining lymph nodes, often allowing time for serious infection to develop. These responses imprint effectors with the capacity to home to infected tissues; this process, combined with inflammatory signals, ensures the effective targeting of primary immunity. Upon vaccination or previous pathogen exposure, increased pathogen-specific T cell numbers together with altered migratory patterns of memory T cells can greatly improve immune efficacy, ensuring infections are prevented or at least remain subclinical. Until recently, memory T cell populations were considered to comprise central memory T cells (TCM), which are restricted to the secondary lymphoid tissues and blood, and effector memory T cells (TEM), which broadly migrate between peripheral tissues, the blood, and the spleen. Here we review evidence for these two memory populations, highlight a relatively new player, the tissue-resident memory T cell (TRM), and emphasize the potential differences between the migratory patterns of CD4(+) and CD8(+) T cells. This new understanding raises important considerations for vaccine design and for the measurement of immune parameters critical to the control of infectious disease, autoimmunity, and cancer.
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              Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs.

              Much has been learned about how cells enter lymphoid tissues. But how do they leave? Sphingosine-1-phosphate (S1P) has emerged over the past decade as a central mediator of lymphocyte egress. In this review, we summarize the current understanding of how S1P promotes exit from the secondary lymphoid organs and thymus. We review what is known about additional requirements for emigration and summarize the mostly distinct requirements for exit from the bone marrow. Egress from lymphoid organs is limited during immune responses, and we examine how this regulation works. There is accumulating evidence for roles of S1P in directing immune cell behavior within lymphoid tissues. How such actions can fit together with the egress-promoting role of S1P is discussed. Finally, we examine current understanding of how FTY720, a drug that targets S1P receptors and is approved for the treatment of multiple sclerosis, causes immune suppression.
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                Author and article information

                Journal
                Nature Medicine
                Nat Med
                Springer Science and Business Media LLC
                1078-8956
                1546-170X
                July 2015
                June 29 2015
                July 2015
                : 21
                : 7
                : 688-697
                Article
                10.1038/nm.3883
                26121195
                4993a4f1-2fa4-445e-85d9-0c8de0061442
                © 2015

                http://www.springer.com/tdm

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