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

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.

scholarly journals Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection

2015 ◽  
Vol 212 (9) ◽  
pp. 1405-1414 ◽  
Author(s):  
Nelson D. Glennie ◽  
Venkata A. Yeramilli ◽  
Daniel P. Beiting ◽  
Susan W. Volk ◽  
Casey T. Weaver ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Leishmania Major ◽  
Memory T Cells ◽  
Critical Role ◽  
Parasitic Infection ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Circulating T Cells ◽  
Memory Cd4 T Cells

Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. Although circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFN-γ and remain resident in the skin when transplanted by skin graft onto naive mice. They function to recruit circulating T cells to the skin in a CXCR3-dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells.

scholarly journals Resident Memory T Cells and Their Role within the Liver

2020 ◽  
Vol 21 (22) ◽  
pp. 8565
Author(s):  
Sonia Ghilas ◽  
Ana-Maria Valencia-Hernandez ◽  
Matthias H. Enders ◽  
William R. Heath ◽  
Daniel Fernandez-Ruiz
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Plasmodium Species ◽  
Immunological Memory ◽  
Cellular Responses ◽  
The Body ◽  
Entire Body ◽  
Memory Cells ◽  
Peripheral Tissues ◽  
Resident Memory T Cells

Immunological memory is fundamental to maintain immunity against re-invading pathogens. It is the basis for prolonged protection induced by vaccines and can be mediated by humoral or cellular responses—the latter largely mediated by T cells. Memory T cells belong to different subsets with specialized functions and distributions within the body. They can be broadly separated into circulating memory cells, which pace the entire body through the lymphatics and blood, and tissue-resident memory T (TRM) cells, which are constrained to peripheral tissues. Retained in the tissues where they form, TRM cells provide a frontline defense against reinfection. Here, we review this population of cells with specific attention to the liver, where TRM cells have been found to protect against infections, in particular those by Plasmodium species that cause malaria.

Expression pattern of tissue-resident memory T cells in cutaneous lupus erythematosus

Lupus ◽  
2021 ◽  
pp. 096120332110172
Author(s):  
Hyeon-Jung Gu ◽  
Shinyoung Song ◽  
Joo Young Roh ◽  
YunJae Jung ◽  
Hee Joo Kim
Keyword(s):  
T Cells ◽  
Lupus Erythematosus ◽  
Memory T Cells ◽  
Cutaneous Lupus Erythematosus ◽  
Discoid Lupus Erythematosus ◽  
Type I ◽  
Systemic Lupus ◽  
Peripheral Tissues ◽  
Resident Memory T Cells ◽  
Cutaneous Lupus

Background Tissue resident memory T cells (TRMs) persist long-term in peripheral tissues without recirculation, triggering an immediate protective inflammatory state upon the re-recognition of the antigen. Despite evidence incriminating the dysregulation of TRMs in autoimmune diseases, few studies have examined their expression in cutaneous lupus erythematosus (CLE). Objectives We aimed to examine whether there are differences among TRM populations in CLE depending on different clinical conditions, such as the CLE subtype or association with systemic lupus erythematosus, and to determine the effect of type I interferon (IFN) on the development of TRMs in CLE. Methods CLE disease activity was evaluated using the Cutaneous Lupus Erythematosus Disease Area and Severity Index. The expression of the TRM markers CD69 and CD103 in CLE lesions was evaluated by immunofluorescence. Flow cytometry was performed on peripheral blood mononuclear cells after IFNα treatment. Results The number of TRMs expressing either CD69 or CD103 was significantly higher in CLE lesions than in control skin; however, it was not significantly different between discoid lupus erythematosus and subacute CLE, or dependent on the presence of concomitant systemic lupus. Lesional severity was not correlated with an increase in TRMs in CLE. IFNα treatment induced a conspicuous increase in CD69 expression in skin-homing T cells, more profoundly in CD4+ T cells than in CD8+ T cells. Conclusions Skin TRMs, either CD69 or CD103-positive cells, showed increased levels in the lesional skin of CLE, and IFNα increased the expression of CD69 in T cells.

scholarly journals Exploring inflammatory signatures in arthritic joint biopsies with Spatial Transcriptomics

2019 ◽  
Vol 9 (1) ◽  
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.

scholarly journals Toxic epidermal necrolysis in the absence of circulating T cells: A possible role for resident memory T cells

2014 ◽  
Vol 71 (5) ◽  
pp. e214-e216 ◽  
Author(s):  
Hisato Iriki ◽  
Takeya Adachi ◽  
Mariko Mori ◽  
Keiji Tanese ◽  
Takeru Funakoshi ◽  
...  
Keyword(s):  
T Cells ◽  
Toxic Epidermal Necrolysis ◽  
Memory T Cells ◽  
Circulating T Cells ◽  
Resident Memory T Cells

scholarly journals Tissue-resident memory T cells in tumor immunity and immunotherapy

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
Karolina Okła ◽  
Donna L. Farber ◽  
Weiping Zou
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Tumor Immunity ◽  
Memory T Cells ◽  
Protective Role ◽  
Peripheral Tissues ◽  
Patients With Cancer ◽  
Favorable Clinical Outcome ◽  
Resident Memory T Cells

Tissue-resident memory T cells (TRM) represent a heterogeneous T cell population with the functionality of both effector and memory T cells. TRM express residence gene signatures. This feature allows them to traffic to, reside in, and potentially patrol peripheral tissues, thereby enforcing an efficient long-term immune-protective role. Recent studies have revealed TRM involvement in tumor immune responses. TRM tumor infiltration correlates with enhanced response to current immunotherapy and is often associated with favorable clinical outcome in patients with cancer. Thus, targeting TRM may lead to enhanced cancer immunotherapy efficacy. Here, we review and discuss recent advances on the nature of TRM in the context of tumor immunity and immunotherapy.

scholarly journals P007 Identification and characterisation of intestine-derived circulating resident memory T cells (ex-Trm) in health and Inflammatory Bowel Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S128-S128
Author(s):  
B Rodger ◽  
I Hoti ◽  
H Gordon ◽  
J Lindsay ◽  
A Stagg
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Intestinal Inflammation ◽  
Memory T Cells ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Tissues ◽  
Resident Memory T Cells

Abstract Background Tissue resident memory T cells (Trm) persist in peripheral tissues where they protect against pathogens but can also contribute to inflammatory disease. Recent work shows that Trm can re-enter the circulation and give rise to new effector T cell and Trm populations in secondary tissue sites. Such ‘ex -Trm’ derived from the skin co-express the residency marker CD103 with cutaneous leukocyte antigen (CLA), a marker associated with skin tropism. Many T cells in the human intestine are Trm but it is unknown whether these cells re-enter the circulation; the existence of gut-derived ex-Trm would have important implications for IBD treatment targeting the recruitment of circulating gut-homing cells. Here, we identify a population of blood cells that co-express CD103 and the gut-homing integrin a4b7 and determine how they are changed in IBD. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and patients with active IBD (Crohn’s disease or ulcerative colitis). Cell surface staining and multi-colour flow cytometry were used to identify CD4+ and CD8+ subsets of antigen experienced (CD45RA-) conventional T cells (abTCR+) and determine expression of markers associated with tissue tropism and residency. Results Staining with antibodies to CD103 and b7 integrin were used to define CD103b7+a4b7+ putative gut ex-Trm based on the excess per cell expression of b7 resulting from its contribution to both integrins. A separate CD103b7+a4b7- population defined by 1:1 expression of CD103 and b7 contained CLA+ skin ex-Trm. Gut ex-Trm comprised 0.3% total circulating CD8+ T cells (range 0.02–1.4%), and 1.2% CD4+ T cells (range 0.3–3%). Gut and skin ex-Trm were phenotypically similar; both expressed the residency associated markers CD101 and CD9 but lacked expression of CD69. Gut ex-Trm were phenotypically distinct from both traditional CD103-a4b7+ gut tropic CD45RA- antigen-experienced T cells and naïve T cells; significantly more gut ex-Trm expressed CD101 and CD9 and fewer expressed CD27. The proportion of gut ex-Trm did not differ between heath and IBD. However, the ratio of gut:skin ex Trm was significantly reduced in active Crohn’s disease but not ulcerative colitis indicating a selective reduction in the population derived from the intestine. Conclusion A putative population of gut-derived ex-Trm can be identified in the blood of healthy controls and IBD patients. This population has a distinctive phenotype similar to that of previously described skin-derived ex-Trm. Circulating ex-Trm could link discreet areas of intestinal inflammation in Crohn’s disease and there is a selective loss of the gut ex-Trm population from the blood of these patients. The role of ex-Trm in IBD merits further study.

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

Cells ◽  
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.

scholarly journals Resident Memory T Cells in Autoimmune Skin Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Grace E. Ryan ◽  
John E. Harris ◽  
Jillian M. Richmond
Keyword(s):  
T Cells ◽  
Lupus Erythematosus ◽  
Skin Diseases ◽  
Memory T Cells ◽  
Cutaneous Lupus Erythematosus ◽  
The Body ◽  
Specific Response ◽  
Peripheral Tissues ◽  
Skin Conditions ◽  
Resident Memory T Cells

Tissue resident memory T cells (TRM) are a critical component of the immune system, providing the body with an immediate and highly specific response against pathogens re-infecting peripheral tissues. More recently, however, it has been demonstrated that TRM cells also form during autoimmunity. TRM mediated autoimmune diseases are particularly destructive, because unlike foreign antigens, the self-antigens are never cleared, continuously activating self-reactive TRM T cells. In this article, we will focus on how TRMs mediate disease in autoimmune skin conditions, specifically vitiligo, psoriasis, cutaneous lupus erythematosus, alopecia areata and frontal fibrosing alopecia.

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