Accumulation and activation of epidermal γδ T cells in a mouse model of chronic dermatitis is not required for the inflammatory phenotype

2015 ◽  
Vol 45 (9) ◽  
pp. 2517-2528 ◽  
Author(s):  
Jitka Sulcova ◽  
Luigi Maddaluno ◽  
Michael Meyer ◽  
Sabine Werner
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Γδ T Cells ◽  
Inflammatory Phenotype

An obligate role for T-cell receptor αβ+ T cells but not T-cell receptor γδ+ T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis

2001 ◽  
Vol 107 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Amy L. Woodward ◽  
Jonathan M. Spergel ◽  
Harri Alenius ◽  
Emiko Mizoguchi ◽  
Atul K. Bhan ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
B Cells ◽  
Mouse Model ◽  
T Cell Receptor ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Αβ T Cells

scholarly journals Itch−/−αβ and γδ T cells independently contribute to autoimmunity in Itchy mice

Blood ◽  
2008 ◽  
Vol 111 (8) ◽  
pp. 4273-7282 ◽  
Author(s):  
Valentino Parravicini ◽  
Anne-Christine Field ◽  
Peter D. Tomlinson ◽  
M. Albert Basson ◽  
Rose Zamoyska
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Microbial Pathogens ◽  
Interleukin 4 ◽  
Cell Subpopulation ◽  
Inflammatory Condition ◽  
Independent Manner ◽  
Autoimmune Pathology ◽  
Inflammatory Phenotype ◽  
Αβ T Cells

Abstract E3 ubiquitin ligases determine which intracellular proteins are targets of the ubiquitin conjugation pathway and thus play a key role in determining the half-life, subcellular localization and/or activation status of their target proteins. Itchy mice lack the E3 ligase, Itch, and show dysregulation of T lymphocytes and the induction of a lethal autoimmune inflammatory condition. Itch is widely expressed in hematopoietic and nonhematopoietic cells, and we demonstrate that disease is transferred exclusively by hematopoietic cells. Moreover, distinct manifestations of the autoimmune inflammatory phenotype are contributed by discrete populations of lymphocytes. The presence of Itch-deficient αβ T cells drives expansion of peritoneal B1b cells and elevated IgM levels, which correlate with itching and pathology. In contrast, Itch−/− interleukin-4–producing γδ T cells, even in the absence of αβ T cells, are associated with elevated levels of IgE and an inflammatory condition. These data indicate that disruption of an E3 ubiquitin ligase in αβ T cells can subvert a B-cell subpopulation, which normally functions to control particular microbial pathogens in a T-independent manner, to contribute to autoimmunity. In addition, disruption of Itch in innate γδ T cells can influence autoimmune pathology and might therefore require distinct therapeutic intervention.

scholarly journals Overload of the Temporomandibular Joints Accumulates γδ T Cells in a Mouse Model of Rheumatoid Arthritis: A Morphological and Histological Evaluation

2022 ◽  
Vol 12 ◽  
Author(s):  
Kohei Nagai ◽  
Takenobu Ishii ◽  
Tatsukuni Ohno ◽  
Yasushi Nishii
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Mouse Model ◽  
Mandibular Condyle ◽  
Γδ T Cells ◽  
Histological Evaluation ◽  
Micro Ct ◽  
Layer Width ◽  
Temporomandibular Joints ◽  
Histological Staining

Recently, it has been reported that γδ T cells are associated with the pathology of rheumatoid arthritis (RA). However, there are many uncertainties about their relationship. In this study, we investigated the morphological and histological properties of peripheral as well as temporomandibular joints (TMJ) in a mouse model of rheumatoid arthritis with and without exposure to mechanical strain on the TMJ. Collagen antibody-induced arthritis (CAIA) was induced by administering collagen type II antibody and lipopolysaccharide to male DBA/1JNCrlj mice at 9−12 weeks of age, and mechanical stress (MS) was applied to the mandibular condyle. After 14 days, 3D morphological evaluation by micro-CT, histological staining (Hematoxylin Eosin, Safranin O, and Tartrate-Resistant Acid Phosphatase staining), and immunohistochemical staining (ADAMTS-5 antibody, CD3 antibody, CD45 antibody, RORγt antibody, γδ T cell receptor antibody) were performed. The lower jawbone was collected. The mandibular condyle showed a rough change in the surface of the mandibular condyle based on three-dimensional analysis by micro-CT imaging. Histological examination revealed bone and cartilage destruction, such as a decrease in chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. Then, immune-histological staining revealed accumulation of T and γδ T cells in the subchondral bone. The temporomandibular joint is less sensitive to the onset of RA, but it has been suggested that it is exacerbated by mechanical stimulation. Additionally, the involvement of γδ T cells was suggested as the etiology of rheumatoid arthritis.

scholarly journals Protective Immunosurveillance and Therapeutic Antitumor Activity of γδ T Cells Demonstrated in a Mouse Model of Prostate Cancer

2008 ◽  
Vol 180 (9) ◽  
pp. 6044-6053 ◽  
Author(s):  
Zhiyong Liu ◽  
Isam-Eldin A. Eltoum ◽  
Ben Guo ◽  
Benjamin H. Beck ◽  
Gretchen A. Cloud ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Antitumor Activity ◽  
Mouse Model ◽  
Γδ T Cells

scholarly journals Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model

2020 ◽  
Author(s):  
Seungjin Ryu ◽  
Irina Shchukina ◽  
Yun-Hee Youm ◽  
Hua Qing ◽  
Brandon K. Hilliard ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Ketogenic Diet ◽  
Systemic Inflammation ◽  
Γδ T Cells ◽  
Inflammasome Activation ◽  
List Type ◽  
Aged Mice ◽  
Risk Of Death ◽  
Coronavirus Infection

SUMMARYIncreasing age is the strongest predictor of risk of COVID-19 severity. Unregulated cytokine storm together with impaired immunometabolic response leads to highest mortality in elderly infected with SARS-CoV-2. To investigate how aging compromises defense against COVID-19, we developed a model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain MHV-A59 (mCoV-A59) that recapitulated majority of clinical hallmarks of COVID-19. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Ketogenic diet increases beta-hydroxybutyrate, expands tissue protective γδ T cells, deactivates the inflammasome and decreases pathogenic monocytes in lungs of infected aged mice. These data underscore the value of mCoV-A59 model to test mechanism and establishes harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against COVID-19 in the elderly.Highlights-Natural MHV-A59 mouse coronavirus infection mimics COVID-19 in elderly.-Aged infected mice have systemic inflammation and inflammasome activation-Murine beta coronavirus (mCoV) infection results in loss of pulmonary γδ T cells.-Ketones protect aged mice from infection by reducing inflammation.eTOC BlurbElderly have the greatest risk of death from COVID-19. Here, Ryu et al report an aging mouse model of coronavirus infection that recapitulates clinical hallmarks of COVID-19 seen in elderly. The increased severity of infection in aged animals involved increased inflammasome activation and loss of γδ T cells that was corrected by ketogenic diet.

scholarly journals Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and antitumor immunity

2019 ◽  
Vol 216 (6) ◽  
pp. 1359-1376 ◽  
Author(s):  
Benjamin D. Medina ◽  
Mengyuan Liu ◽  
Gerardo A. Vitiello ◽  
Adrian M. Seifert ◽  
Shan Zeng ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Cd8 T Cells ◽  
Antitumor Immunity ◽  
Γδ T Cells ◽  
Imatinib Treatment ◽  
Kinase Inhibition ◽  
Gm Csf ◽  
T Cell Infiltration ◽  
Activating Mutation

Gastrointestinal stromal tumor (GIST) is driven by an activating mutation in the KIT proto-oncogene. Using a mouse model of GIST and human specimens, we show that intratumoral murine CD103+CD11b− dendritic cells (DCs) and human CD141+ DCs are associated with CD8+ T cell infiltration and differentiation. In mice, the antitumor effect of the Kit inhibitor imatinib is partially mediated by CD103+CD11b− DCs, and effector CD8+ T cells initially proliferate. However, in both mice and humans, chronic imatinib therapy decreases intratumoral DCs and effector CD8+ T cells. The mechanism in our mouse model depends on Kit inhibition, which reduces intratumoral GM-CSF, leading to the accumulation of Batf3-lineage DC progenitors. GM-CSF is produced by γδ T cells via macrophage IL-1β. Stimulants that expand and mature DCs during imatinib treatment improve antitumor immunity. Our findings identify the importance of tumor cell oncogene activity in modulating the Batf3-dependent DC lineage and reveal therapeutic limitations for combined checkpoint blockade and tyrosine kinase inhibition.

scholarly journals Interleukin 17, Produced by γδ T Cells, Contributes to Hepatic Inflammation in a Mouse Model of Biliary Atresia and Is Increased in Livers of Patients

2016 ◽  
Vol 150 (1) ◽  
pp. 229-241.e5 ◽  
Author(s):  
Christian Klemann ◽  
Arne Schröder ◽  
Anika Dreier ◽  
Nora Möhn ◽  
Stephanie Dippel ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Biliary Atresia ◽  
Γδ T Cells ◽  
Interleukin 17 ◽  
Hepatic Inflammation

scholarly journals Endogenous IL-22 is dispensable for experimental glomerulonephritis

2019 ◽  
Vol 316 (4) ◽  
pp. F712-F722 ◽  
Author(s):  
Ann-Christin Gnirck ◽  
Malte Wunderlich ◽  
Martina Becker ◽  
Tingting Xiong ◽  
Ella Weinert ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Γδ T Cells ◽  
Tubular Damage ◽  
Glomerular Injury ◽  
Crescent Formation ◽  
Phenotypic Differences ◽  
Renal Tubular ◽  
Barrier Tissues

In recent years, the cytokine interleukin (IL)-22 attracted considerable attention due to its important immunoregulatory function in barrier tissues, such as the gut, lung, and skin. Although a regenerative role of IL-22 in renal tubular damage has been demonstrated, the role of IL-22 in the immunopathogenesis of glomerular injury is still unknown. Here, we demonstrate that the IL-22 receptor is expressed in the glomerular compartment of the kidney and that IL-22 expression increases in the renal cortex after induction of glomerular injury in a mouse model for crescentic glomerulonephritis (cGN, nephrotoxic nephritis). We identified γδ T cells and TH17 cells as major sources for IL-22 in the nephritic kidney. However, neither genetic or antibody-mediated deletion of IL-22 nor genetic deficiency in its endogenous inhibitor IL-22Rα2 (IL-22 binding protein) resulted in substantial phenotypic differences in mice with cGN with respect to crescent formation, tubulointerstitial damage, and kidney function impairment. Similarly, we did not observe significant differences between wild-type or IL-22-deficient mice in a mouse model of secondary focal and segmental glomerulosclerosis (adriamycin-induced nephropathy). As shown previously, we detected concomitant upregulation of IL-17A and IFN-γ production by T cells during the course of cGN, providing alternative cytokine pathways that mediate glomerular injury in this model. In conclusion, we show here that endogenous IL-22 expression is redundant in different forms of glomerular injury, indicating that the IL-22-directed therapies that are being tested in various human diseases might not affect the kidney in patients with glomerular disease.

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