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.

scholarly journals The Role of Tissue-resident γδ T Cells in Stress Surveillance and Tissue Maintenance

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 686 ◽  
Author(s):  
Margarete D. Johnson ◽  
Deborah A. Witherden ◽  
Wendy L. Havran
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
Intestinal Epithelium ◽  
Γδ T Cells ◽  
Minor Population ◽  
A Minor ◽  
And Function ◽  
Protection Against Infection ◽  
Barrier Tissues

While forming a minor population in the blood and lymphoid compartments, γδ T cells are significantly enriched within barrier tissues. In addition to providing protection against infection, these tissue-resident γδ T cells play critical roles in tissue homeostasis and repair. γδ T cells in the epidermis and intestinal epithelium produce growth factors and cytokines that are important for the normal turnover and maintenance of surrounding epithelial cells and are additionally required for the efficient recognition of, and response to, tissue damage. A role for tissue-resident γδ T cells is emerging outside of the traditional barrier tissues as well, with recent research indicating that adipose tissue-resident γδ T cells are required for the normal maintenance and function of the adipose tissue compartment. Here we review the functions of tissue-resident γδ T cells in the epidermis, intestinal epithelium, and adipose tissue, and compare the mechanisms of their activation between these sites.

scholarly journals The role of unconventional T cells in COVID-19

2021 ◽  
Author(s):  
Kristen Orumaa ◽  
Margaret R. Dunne
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Treatment Strategies ◽  
Γδ T Cells ◽  
Protective Role ◽  
T Cell Subsets ◽  
Viral Immunity ◽  
Mait Cells

AbstractCOVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first documented in late 2019, but within months, a worldwide pandemic was declared due to the easily transmissible nature of the virus. Research to date on the immune response to SARS-CoV-2 has focused largely on conventional B and T lymphocytes. This review examines the emerging role of unconventional T cell subsets, including γδ T cells, invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells in human SARS-CoV-2 infection.Some of these T cell subsets have been shown to play protective roles in anti-viral immunity by suppressing viral replication and opsonising virions of SARS-CoV. Here, we explore whether unconventional T cells play a protective role in SARS-CoV-2 infection as well. Unconventional T cells are already under investigation as cell-based immunotherapies for cancer. We discuss the potential use of these cells as therapeutic agents in the COVID-19 setting. Due to the rapidly evolving situation presented by COVID-19, there is an urgent need to understand the pathogenesis of this disease and the mechanisms underlying its immune response. Through this, we may be able to better help those with severe cases and lower the mortality rate by devising more effective vaccines and novel treatment strategies.

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

Role of γδ T cells in Behcet's disease

The Lancet ◽  
1996 ◽  
Vol 347 (9015) ◽  
pp. 1631-1632 ◽  
Author(s):  
J.S.H. Gaston ◽  
Adam Hasan ◽  
Farida Fortune ◽  
Amanda Wilson ◽  
Thomas Lehner
Keyword(s):  
T Cells ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Γδ T Cells ◽  
Behcet's Disease

Evidence for a role of γδ T cells in demyelinating diseases as determined by activation states and responses to lipid antigens

2000 ◽  
Vol 107 (2) ◽  
pp. 124-129 ◽  
Author(s):  
G Borsellino ◽  
O Koul ◽  
R Placido ◽  
D Tramonti ◽  
S Luchetti ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Demyelinating Diseases ◽  
Lipid Antigens

Abstract 12: The Role Of Memory Gamma Delta T Cells In Hypertension And Vascular Damage

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Kevin D Comeau ◽  
Pierre Paradis ◽  
Ernesto L Schiffrin
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
Γδ T Cells ◽  
Effector Memory ◽  
Ang Ii ◽  
Mesenteric Lymph Nodes ◽  
Initial Exposure ◽  
Perivascular Adipose Tissue ◽  
Mild Hypertensive

Background: We recently demonstrated that γδ T cells participate in the pathogenesis of hypertension. Evidence also suggests that memory T cells may develop during an initial hypertensive episode, sensitizing mice to develop hypertension to further mild hypertensive challenges. However, whether memory γδ T cells develop and play a role in hypertension remains unknown. Our objective is to determine if memory γδ T cells sensitize mice to develop hypertension in response to a mild hypertensive challenge. Methods: Ten-12-week-old C57BL/6J mice were exposed or not to a hypertensive challenge (490 ng/kg/min angiotensin II (Ang II), SC) for two weeks, followed by a two-week washout period, and then infused with a subpressor dose of Ang II (140 ng/kg/min Ang II, SC) for two weeks. Blood pressure was measured via telemetry and central, effector, and resident memory γδ T cells were profiled by flow cytometry. Results: Mice exposed to the first hypertensive challenge had a higher systolic blood pressure than the sham group at the end of the subpressor hypertensive challenge (149±6 vs. 122±3 mmHg, P <0.001). After 14-days of Ang II infusion, effector memory γδ T cells increased 5.2-fold in the mesenteric artery perivascular adipose tissue (PVAT, 1.25±0.37% vs. 0.24±0.12%, P <0.05), and 1.8-fold in the mesenteric lymph nodes (mLN, 1.49±0.03% vs. 0.82±0.15%, P <0.05) compared to sham treated mice. After repeated Ang II infusion, central memory γδ T cells decreased by 57% in the aortic PVAT (6.79±1.46% vs. 15.69±2.87%, P <0.05), and by 22% in the mLN (0.18±0.01% vs. 0.23±0.01%, P <0.05) compared to control mice. Conclusion: An initial exposure to a hypertensive stimulus sensitizes mice to develop hypertension to a subsequent subpressor hypertensive challenge and results in the development of memory γδ T cells.

PL1-2. The role of inflammasome processed cytokines in driving Th17 cells and IL-17 producing γδ T cells in infection and autoimmunity

Cytokine ◽  
2011 ◽  
Vol 56 (1) ◽  
pp. 3
Author(s):  
Kingston H.G. Mills ◽  
Aisling Dunne ◽  
Lara Dungan ◽  
Jean Fletcher ◽  
Sarah Higgins ◽  
...  
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Γδ T Cells

scholarly journals T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS

2008 ◽  
Vol 105 (46) ◽  
pp. 17913-17918 ◽  
Author(s):  
Isaac M. Chiu ◽  
Adam Chen ◽  
Yi Zheng ◽  
Bela Kosaras ◽  
Stefanos A. Tsiftsoglou ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Disease Progression ◽  
Cholesterol Metabolism ◽  
Cell Receptor ◽  
Specific Flow ◽  
Innate And Adaptive Immunity ◽  
Expression Of Genes ◽  
Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive, motor neuron degenerative disease, in which the role of inflammation is not well established. Innate and adaptive immunity were investigated in the CNS of the Superoxide Dismutase 1 (SOD1)G93A transgenic mouse model of ALS. CD4+ and CD8+ T cells infiltrated SOD1G93A spinal cords during disease progression. Cell-specific flow cytometry and gene expression profiling showed significant phenotypic changes in microglia, including dendritic cell receptor acquisition, and expression of genes linked to neuroprotection, cholesterol metabolism and tissue remodeling. Microglia dramatically up-regulated IGF-1 and down-regulated IL-6 expression. When mutant SOD1 mice were bred onto a TCRβ deficient background, disease progression was significantly accelerated at the symptomatic stage. In addition, microglia reactivity and IGF-1 levels were reduced in spinal cords of SOD1G93A (TCRβ−/−) mice. These results indicate that T cells play an endogenous neuroprotective role in ALS by modulating a beneficial inflammatory response to neuronal injury.

scholarly journals T Cell Receptor Specificity Is Critical for the Development of Epidermal γδ T Cells

2001 ◽  
Vol 194 (10) ◽  
pp. 1473-1483 ◽  
Author(s):  
Isabel Ferrero ◽  
Anne Wilson ◽  
Friedrich Beermann ◽  
Werner Held ◽  
H. Robson MacDonald
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Biology ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Wild Type ◽  
Normal Numbers ◽  
T Cell Biology

A particular feature of γδ T cell biology is that cells expressing T cell receptor (TCR) using specific Vγ/Vδ segments are localized in distinct epithelial sites, e.g., in mouse epidermis nearly all γδ T cells express Vγ3/Vδ1. These cells, referred to as dendritic epidermal T cells (DETC) originate from fetal Vγ3+ thymocytes. The role of γδ TCR specificity in DETC's migration/localization to the skin has remained controversial. To address this issue we have generated transgenic (Tg) mice expressing a TCR δ chain (Vδ6.3-Dδ1-Dδ2-Jδ1-Cδ), which can pair with Vγ3 in fetal thymocytes but is not normally expressed by DETC. In wild-type (wt) Vδ6.3Tg mice DETC were present and virtually all of them express Vδ6.3. However, DETC were absent in TCR-δ−/− Vδ6.3Tg mice, despite the fact that Vδ6.3Tg γδ T cells were present in normal numbers in other lymphoid and nonlymphoid tissues. In wt Vδ6.3Tg mice, a high proportion of in-frame Vδ1 transcripts were found in DETC, suggesting that the expression of an endogenous TCR-δ (most probably Vδ1) was required for the development of Vδ6.3+ epidermal γδ T cells. Collectively our data demonstrate that TCR specificity is essential for the development of γδ T cells in the epidermis. Moreover, they show that the TCR-δ locus is not allelically excluded.

scholarly journals Emerging role of γδ T cells in vaccine‐mediated protection from infectious diseases

2019 ◽  
Vol 8 (8) ◽  
Author(s):  
Kathleen W Dantzler ◽  
Lauren Parte ◽  
Prasanna Jagannathan
Keyword(s):  
T Cells ◽  
Infectious Diseases ◽  
Γδ T Cells
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