Tissue–Resident Memory T Cells in Chronic Inflammation—Local Cells with Systemic Effects?

Anoushka Ashok Kumar Samat; Jolijn van der Geest; Sebastiaan J. Vastert; Jorg van Loosdregt; Femke van Wijk

doi:10.3390/cells10020409

Tissue–Resident Memory T Cells in Chronic Inflammation—Local Cells with Systemic Effects?

Cells ◽

10.3390/cells10020409 ◽

2021 ◽

Vol 10 (2) ◽

pp. 409

Author(s):

Anoushka Ashok Kumar Samat ◽

Jolijn van der Geest ◽

Sebastiaan J. Vastert ◽

Jorg van Loosdregt ◽

Femke van Wijk

Keyword(s):

Gene Expression ◽

T Cells ◽

Chronic Inflammation ◽

Memory T Cells ◽

Inflammatory Diseases ◽

Chronic Inflammatory Disease ◽

Chronic Inflammatory Diseases ◽

Recent Developments ◽

Resident Memory T Cells ◽

Barrier Tissues

Chronic inflammatory diseases such as rheumatoid arthritis (RA), Juvenile Idiopathic Arthritis (JIA), psoriasis, and inflammatory bowel disease (IBD) are characterized by systemic as well as local tissue inflammation, often with a relapsing-remitting course. Tissue–resident memory T cells (TRM) enter non-lymphoid tissue (NLT) as part of the anamnestic immune response, especially in barrier tissues, and have been proposed to fuel chronic inflammation. TRM display a distinct gene expression profile, including upregulation of CD69 and downregulation of CD62L, CCR7, and S1PR1. However, not all TRM are consistent with this profile, and it is now more evident that the TRM compartment comprises a heterogeneous population, with differences in their function and activation state. Interestingly, the paradigm of TRM remaining resident in NLT has also been challenged. T cells with TRM characteristics were identified in both lymph and circulation in murine and human studies, displaying similarities with circulating memory T cells. This suggests that re-activated TRM are capable of retrograde migration from NLT via differential gene expression, mediating tissue egress and circulation. Circulating ‘ex-TRM’ retain a propensity for return to NLT, especially to their tissue of origin. Additionally, memory T cells with TRM characteristics have been identified in blood from patients with chronic inflammatory disease, leading to the hypothesis that TRM egress from inflamed tissue as well. The presence of TRM in both tissue and circulation has important implications for the development of novel therapies targeting chronic inflammation, and circulating ‘ex-TRM’ may provide a vital diagnostic tool in the form of biomarkers. This review elaborates on the recent developments in the field of TRM in the context of chronic inflammatory diseases.

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Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective

Journal of Experimental Medicine ◽

10.1084/jem.20191123 ◽

2019 ◽

Vol 217 (1) ◽

Cited By ~ 11

Author(s):

Pascale Zwicky ◽

Susanne Unger ◽

Burkhard Becher

Keyword(s):

Rheumatoid Arthritis ◽

Inflammatory Diseases ◽

Chronic Inflammatory Disease ◽

Interleukin 17 ◽

Clinical Perspective ◽

Preclinical Models ◽

Chronic Inflammatory Diseases ◽

Recent Developments ◽

Disease Entities ◽

Barrier Tissues

Chronic inflammatory diseases like psoriasis, Crohn’s disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), and others are increasingly recognized as disease entities, where dysregulated cytokines contribute substantially to tissue-specific inflammation. A dysregulation in the IL-23/IL-17 axis can lead to inflammation of barrier tissues, whereas its role in internal organ inflammation remains less clear. Here we discuss the most recent developments in targeting IL-17 for the treatment of chronic inflammation in preclinical models and in patients afflicted with chronic inflammatory diseases.

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Exploring inflammatory signatures in arthritic joint biopsies with Spatial Transcriptomics

Scientific Reports ◽

10.1038/s41598-019-55441-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 7

Author(s):

Konstantin Carlberg ◽

Marina Korotkova ◽

Ludvig Larsson ◽

Anca I. Catrina ◽

Patrik L. Ståhl ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

Immune Cell ◽

Memory T Cells ◽

Inflammatory Diseases ◽

Adaptive Immune Response ◽

Cell Types ◽

Effector Memory ◽

Cellular Mechanisms ◽

Chronic Inflammatory Diseases

AbstractLately it has become possible to analyze transcriptomic profiles in tissue sections with retained cellular context. We aimed to explore synovial biopsies from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients, using Spatial Transcriptomics (ST) as a proof of principle approach for unbiased mRNA studies at the site of inflammation in these chronic inflammatory diseases. Synovial tissue biopsies from affected joints were studied with ST. The transcriptome data was subjected to differential gene expression analysis (DEA), pathway analysis, immune cell type identification using Xcell analysis and validation with immunohistochemistry (IHC). The ST technology allows selective analyses on areas of interest, thus we analyzed morphologically distinct areas of mononuclear cell infiltrates. The top differentially expressed genes revealed an adaptive immune response profile and T-B cell interactions in RA, while in SpA, the profiles implicate functions associated with tissue repair. With spatially resolved gene expression data, overlaid on high-resolution histological images, we digitally portrayed pre-selected cell types in silico. The RA displayed an overrepresentation of central memory T cells, while in SpA effector memory T cells were most prominent. Consequently, ST allows for deeper understanding of cellular mechanisms and diversity in tissues from chronic inflammatory diseases.

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Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

Journal of Clinical Medicine ◽

10.3390/jcm10173822 ◽

2021 ◽

Vol 10 (17) ◽

pp. 3822

Author(s):

Trung T. Vu ◽

Hanako Koguchi-Yoshioka ◽

Rei Watanabe

Keyword(s):

T Cells ◽

Memory T Cells ◽

Inflammatory Diseases ◽

Adaptive Immune Response ◽

Psoriatic Skin ◽

Peripheral Tissues ◽

Potential Index ◽

Circulating T Cells ◽

Chronic Skin ◽

Resident Memory T Cells

Tissue-resident memory T cells (TRM) stay in the peripheral tissues for long periods of time, do not recirculate, and provide the first line of adaptive immune response in the residing tissues. Although TRM originate from circulating T cells, TRM are physiologically distinct from circulating T cells with the expression of tissue-residency markers, such as CD69 and CD103, and the characteristic profile of transcription factors. Besides defense against pathogens, the functional skew of skin TRM is indicated in chronic skin inflammatory diseases. In psoriasis, IL-17A-producing CD8+ TRM are regarded as one of the pathogenic populations in skin. Although no licensed drugs that directly and specifically inhibit the activity of skin TRM are available to date, psoriatic skin TRM are affected in the current treatments of psoriasis. Targeting skin TRM or using TRM as a potential index for disease severity can be an attractive strategy in psoriasis.

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Calcium Signaling in T Cells and Chronic Inflammatory Disorders of the Oral Cavity

Journal of Dental Research ◽

10.1177/0022034521990652 ◽

2021 ◽

pp. 002203452199065

Author(s):

S. Hasiakos ◽

Y. Gwack ◽

M. Kang ◽

I. Nishimura

Keyword(s):

T Cells ◽

T Cell ◽

Oral Cavity ◽

Calcium Signaling ◽

Signaling Pathways ◽

Chronic Inflammation ◽

Th17 Cells ◽

Inflammatory Diseases ◽

Chronic Inflammatory Diseases

Acute immune responses to microbial insults in the oral cavity often progress to chronic inflammatory diseases such as periodontitis and apical periodontitis. Chronic oral inflammation causes destruction of the periodontium, potentially leading to loss of the dentition. Previous investigations have demonstrated that the composition of oral immune cells, rather than the overall extent of cellular infiltration, determines the pathological development of chronic inflammation. The role of T lymphocyte populations, including Th1, Th2, Th17, and Treg cells, has been extensively described. Studies now propose pathogenic Th17 cells as a distinct subset, uniquely classifiable from traditional Th17 populations. In situ differentiation of pathogenic Th17 cells has been verified as a source of destructive inflammation, which critically drives pathogenesis in chronic inflammatory diseases such as diabetes, rheumatoid arthritis, and inflammatory bowel disease. Pathogenic Th17 cells resemble a Th1 penotype and produce not only interleukin 17 (IL-17) but also γ-interferon (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The proinflammatory cytokine-specific mechanisms known to induce IL-17 expression in Th17 cells are well characterized; however, differentiation mechanisms that lead to pathogenic Th17 cells are less understood. Recently, Ca2+ signaling through Ca2+ release-activated Ca2+ channels (CRAC) in T cells has been uncovered as a major signaling axis involved in the regulation of T-cell-mediated chronic inflammation. In particular, pathogenic Th17 cell–mediated immunological diseases appear to be effectively targeted via such Ca2+ signaling pathways. Pathogenic plasticity of Th17 cells has been extensively illustrated in autoimmune and chronic inflammatory diseases. Although their specific causal relationship to oral infection-induced chronic inflammatory diseases is not fully established, pathogenic Th17 cells may be involved in the underlining mechanism. This review highlights the current understanding of T-cell phenotype regulation, calcium signaling pathways in this event, and the potential role of pathogenic Th17 cells in chronic inflammatory disorders of the oral cavity.

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Tissue-Resident Memory T Cells in Antifungal Immunity

Frontiers in Immunology ◽

10.3389/fimmu.2021.693055 ◽

2021 ◽

Vol 12 ◽

Author(s):

Salomé LeibundGut-Landmann

Keyword(s):

T Cells ◽

Memory T Cells ◽

Fungal Infections ◽

Fast Response ◽

Host Protection ◽

Mucosal Surfaces ◽

Life Threatening ◽

Epithelial Barriers ◽

Resident Memory T Cells ◽

Barrier Tissues

Fungi are an integral part of the mammalian microbiota colonizing most if not all mucosal surfaces and the skin. Maintaining stable colonization on these surfaces is critical for preventing fungal dysbiosis and infection, which in some cases can lead to life threatening consequences. The epithelial barriers are protected by T cells and additional controlling immune mechanisms. Noncirculating memory T cells that reside stably in barrier tissues play an important role for host protection from commensals and recurrent pathogens due to their fast response and local activity, which provides them a strategic advantage. So far, only a few specific examples of tissue resident memory T cells (TRMs) that act against fungi have been reported. This review provides an overview of the characteristics and functional attributes of TRMs that have been established based on human and mouse studies with various microbes. It highlights what is currently known about fungi specific TRMs mediating immunosurveillance, how they have been targeted in preclinical vaccination approaches and how they can promote immunopathology, if not controlled. A better appreciation of the host protective and damaging roles of TRMs might accelerate the development of novel tissue specific preventive strategies against fungal infections and fungi-driven immunopathologies.

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