scholarly journals Mining the human tonsillar microbiota as autoimmune modulator

2019 ◽  
Author(s):  
Jing Li ◽  
Shenghui Li ◽  
Jiayang Jin ◽  
Ruochun Guo ◽  
Xiaolin Sun ◽  
...  
Keyword(s):  
Autoimmune Disorder ◽  
T Cell Subsets ◽  
Immune Homeostasis ◽  
Antibacterial Peptides ◽  
Streptococcus Salivarius ◽  
Active Components ◽  
Autoantibody Production ◽  
Palatine Tonsils ◽  
Effector T Cell ◽  
First Time

AbstractPalatine tonsils are important lymphoid organs featuring constant cross-talks between the commensal microorganisms and immune system, and have been implicated as critical autoimmunity origins for immune-related diseases, including rheumatoid arthritis (RA), a common autoimmune disorder. However, there was no evidence to show link between tonsillar microbiota and RA. Here, we identified a significant dysbiosis of RA tonsillar microbiota, with loss of Streptococcus salivarius and its functional molecules salivaricins (a type of antibacterial peptides). Consistent with the niche-preference, S. salivarius and salivaricins administrated intranasally or intraorally conferred prophylactic and therapeutic efficacies against experimental arthritis. Moreover, we demonstrated, for the first time, that S. salivarius and salivaricins exerted immunosuppressive capacities via inhibiting CD4+effector T cell subsets and autoantibody production in mice and human. These results uncover a communication between tonsillar microbiota and host autoimmunity, and identify the active components from tonsillar microbes in modulating immune homeostasis.One sentence summaryTonsillar microbiota regulate host autoimmunity via antibacterial peptides

Tocilizumab: An Updated Review of Its Use in the Treatment of Rheumatoid Arthritis and Its Application for Other Immune-Mediated Diseases

2013 ◽  
Vol 5 ◽  
pp. CMT.S9282 ◽  
Author(s):  
Toshio Tanaka ◽  
Atsushi Ogata ◽  
Masashi Narazaki
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
T Cell Subsets ◽  
Unknown Etiology ◽  
Autoantibody Production ◽  
Future Studies ◽  
Effector T Cell ◽  
Immune Mediated ◽  
Cell Source ◽  
Acute Phase Reactions

Interleukin-6 (IL-6), produced by a variety of cells, is a typical cytokine featuring redundancy and pleiotropic activity. IL-6 is promptly and transiently synthesized in response to infections or injuries, and participates in host defense by inducing immune responses, hematopoiesis, and acute-phase reactions. However, since its abnormal persistent production of mostly unknown etiology plays an important pathological role in the development of various immune-mediated diseases, a humanized anti-IL-6 receptor monoclonal antibody, tocilizumab, was developed and is now used as an innovative biologic for rheumatoid arthritis in more than 90 countries. Several factors strongly suggest that a IL-6 blockade strategy may have a broad application for the treatment of various immune-mediated diseases. These factors include favorable results of pilot or case studies with off-label use of tocilizumab, pathological analyses of the contribution of IL-6 to the development of immune-mediated diseases, and the potential capability of tocilizumab to both repair an imbalance of effector T cell subsets and to suppress pathologic autoantibody production. However, clinical trials to evaluate the efficacy and safety of tocilizumab for these diseases are essential. Furthermore, clarification of the cell source of IL-6 production and of the mechanisms through which dysregulated continuous IL-6 synthesis is induced constitutes an important issue for future studies into the pathogenesis of diseases.

Evidence for Associations Between Th1/Th17 “Hybrid” Phenotype and Altered Lipometabolism in Very Severe Graves Orbitopathy

2020 ◽  
Vol 105 (6) ◽  
pp. 1851-1867 ◽  
Author(s):  
Sijie Fang ◽  
Shuo Zhang ◽  
Yazhuo Huang ◽  
Yu Wu ◽  
Yi Lu ◽  
...  
Keyword(s):  
T Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
T Cell Subsets ◽  
Th1 Cell ◽  
Effector T Cell ◽  
Cell Lineages ◽  
Graves Orbitopathy ◽  
Ifn Γ

Abstract Purpose The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. Methods Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. Results In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-γt (RORγt) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced interferon-γ (IFN-γ). Increased IFN-γ–producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-γ–producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. Conclusions Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.

Abstract 424: Effector T Cells Induce Cardiac Fibroblasts Transition to Myofibroblasts & Contribute to Pressure Overload Induced Cardiac Fibrosis

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Tania A Nevers ◽  
Ane Salvador ◽  
Francisco Velazquez ◽  
Mark Aronovitz ◽  
Robert Blanton
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Effector T Cells ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Effector T Cell ◽  
Naïve T Cells

Background: Cardiac fibrogenesis is a major pathogenic factor that occurs in heart failure (HF) and results in contractile dysfunction and ventricular dilation. Recently, we showed that T cell deficient mice (TCRα -/- ) do not develop cardiac fibrosis (CF) and have preserved cardiac function in the thoracic aortic constriction (TAC) mouse model of pressure overload (PO). Specifically, CD4 + T cells are activated in the cardiac draining lymph nodes and infiltrate the LV, where the Th1 and Th17 effector T cell signature transcription factors are significantly upregulated as compared with control mice. However, the T cell subsets involved and the mechanisms by which they contribute to CF and pathogenesis of non-ischemic HF remains to be determined. Thus, we hypothesize that heart infiltrated effector T cells perpetuate the fibrotic response by regulating the differentiation and activation of extracellular matrix-producing cardiac myofibroblasts. Methods and Results: Naïve or effector T cells differentiated in vitro or isolated from mice undergoing TAC or Sham surgery were co-cultured with adult C57BL/6 cardiac fibroblasts (CFB). In contrast with naïve T cells, effector T cells and PO activated T cells strongly adhered to CFB and mediated fibroblast to myofibroblasts transition as depicted by immunofluorescence expression of SMAα. Effector T cell supernatants only slightly mediated this transition, indicating that effector T cells direct contact with CFB, rather than cytokine release is required to mediate CFB transformation. Adoptive transfer of effector, but not naïve T cells, into TCRα -/- recipient mice in the onset of TAC resulted in T cells infiltration into the left ventricle and increased CF. Conclusions: Our data indicate that CD4+ effector T cells directly interact with CFB to induce CF in response to PO induced CF. Future studies will determine the adhesion mechanisms regulating this crosstalk and evaluate the pro-fibrotic mechanisms induced and whether this is a T effector cell specific subset. These results will provide an attractive tool to counteract the inflammatory/fibrotic process as an alternative option for the treatment of CF in non- ischemic HF.

scholarly journals Immune signatures of prodromal multiple sclerosis in monozygotic twins

2020 ◽  
Vol 117 (35) ◽  
pp. 21546-21556 ◽  
Author(s):  
Lisa Ann Gerdes ◽  
Claudia Janoschka ◽  
Maria Eveslage ◽  
Bianca Mannig ◽  
Timo Wirth ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
T Cell Subsets ◽  
Effector T Cell ◽  
Immune Signatures ◽  
Relapsing Remitting ◽  
Immune Traits

The tremendous heterogeneity of the human population presents a major obstacle in understanding how autoimmune diseases like multiple sclerosis (MS) contribute to variations in human peripheral immune signatures. To minimize heterogeneity, we made use of a unique cohort of 43 monozygotic twin pairs clinically discordant for MS and searched for disease-related peripheral immune signatures in a systems biology approach covering a broad range of adaptive and innate immune populations on the protein level. Despite disease discordance, the immune signatures of MS-affected and unaffected cotwins were remarkably similar. Twinship alone contributed 56% of the immune variation, whereas MS explained 1 to 2% of the immune variance. Notably, distinct traits in CD4+effector T cell subsets emerged when we focused on a subgroup of twins with signs of subclinical, prodromal MS in the clinically healthy cotwin. Some of these early-disease immune traits were confirmed in a second independent cohort of untreated early relapsing-remitting MS patients. Early involvement of effector T cell subsets thus points to a key role of T cells in MS disease initiation.

scholarly journals PTCy ameliorates GVHD by restoring regulatory and effector T-cell homeostasis in recipients with PD-1 blockade

2019 ◽  
Vol 3 (23) ◽  
pp. 4081-4094 ◽  
Author(s):  
Shuntaro Ikegawa ◽  
Yusuke Meguri ◽  
Takumi Kondo ◽  
Hiroyuki Sugiura ◽  
Yasuhisa Sando ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Effector T Cells ◽  
T Cell Subsets ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Effector T Cell ◽  
Key Points

Key Points PD-1 blockade exacerbated GVHD by altering the homeostasis of Tregs and effector T cells after HSCT. PTCy ameliorated GVHD after PD-1 blockade by restoring the homeostatic balance of T-cell subsets.

scholarly journals Cytokines and effector T cell subsets causing autoimmune CNS disease

FEBS Letters ◽  
2011 ◽  
Vol 585 (23) ◽  
pp. 3747-3757 ◽  
Author(s):  
Franziska Petermann ◽  
Thomas Korn
Keyword(s):  
T Cell ◽  
T Cell Subsets ◽  
Cns Disease ◽  
Effector T Cell

scholarly journals Triterpenic Acids and Flavonoids from Satureja parvifolia. Evaluation of their Antiprotozoal Activity

2006 ◽  
Vol 61 (3-4) ◽  
pp. 189-192 ◽  
Author(s):  
Catalina van Baren ◽  
Ivie Anao ◽  
Paola Di Leo Lira ◽  
Silvia Debenedetti ◽  
Peter Houghton ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Moderate Activity ◽  
Antiprotozoal Activity ◽  
Active Components ◽  
Trypanosoma Brucei Rhodesiense ◽  
Meoh Extract ◽  
Triterpenic Acids ◽  
Bioassay Guided Fractionation ◽  
Low Cytotoxicity ◽  
First Time

Bioassay-guided fractionation of a Satureja parvifolia MeOH extract led to the isolation of eriodictyol, luteolin and ursolic and oleanolic acids as its active components against Plasmodium falciparum K1. This is the first time these compounds are reported as constituents of S. parvifolia. Ursolic acid showed an IC50 of 4.9 μg/ml, luteolin 6.4 μg/ml, oleanolic acid 9.3 μg/ml and eriodictyol 17.2 μg/ml. Antiplasmodial activity of eriodictyol and luteolin is reported here for the first time. Besides, the four compounds showed activity against P. falciparum 3D7 strain and Trypanosoma brucei rhodesiense. Eriodictyol showed moderate activity on all the parasites but was the most selective compound as a result of its rather low cytotoxicity (IC50 174.2 μg/ml) on the mammalian KB cell line.

scholarly journals Protection by and maintenance of CD4 effector memory and effector T cell subsets in persistent malaria infection

2018 ◽  
Vol 14 (4) ◽  
pp. e1006960 ◽  
Author(s):  
Michael M. Opata ◽  
Samad A. Ibitokou ◽  
Victor H. Carpio ◽  
Karis M. Marshall ◽  
Brian E. Dillon ◽  
...  
Keyword(s):  
T Cell ◽  
Malaria Infection ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Effector T Cell

scholarly journals Unraveling the leaf-dropping behavior behind bat folivory: do bats use biological control against roost parasites?

Mammalia ◽  
2020 ◽  
Vol 84 (2) ◽  
pp. 195-200
Author(s):  
Mariana Muñoz-Romo ◽  
Paolo Ramoni-Perazzi
Keyword(s):  
Biological Control ◽  
Chemical Properties ◽  
Active Components ◽  
Control Behavior ◽  
Liquid Portion ◽  
Important Amount ◽  
Intact Leaves ◽  
Reproductive Processes ◽  
Artibeus Lituratus ◽  
First Time

AbstractFolivory in bats, the behavior of chewing bites of leaves to extract the liquid portion and discard the fiber as oral pellets, is seen as a strategy that might provide vitamins, micronutrients and proteins not always available in fruits, and even secondary metabolites (hormonal precursors) that stimulate/inhibit reproductive processes. While examining chewed leaves, we noticed an important amount of completely intact leaves below the roosts of Artibeus amplus and Artibeus lituratus, and decided to systematically quantify them during a year. We recovered 639 intact leaves from six plant species and found that both species are constantly feeding on leaves, but invariably leaving 26–78% of these intact, dropping them on the floor just below their roosting sites. These large proportions of dropped, intact leaves suggest a completely different, novel, non-nutritional use by bats. Several studies in birds have revealed that fresh leaves are effectively used in nests to control diverse organisms that include blood suckling ectoparasites, protozoans, fungus and bacteria. We report for the first time this biological control behavior performed by bats by selecting, bringing and dropping intact leaves below their roosting sites. The chemical properties of the leaves need to be investigated to reveal those active components against specific pathogens.

scholarly journals CD4 Effector T Cell Subsets in the Response to Influenza

2002 ◽  
Vol 196 (7) ◽  
pp. 957-968 ◽  
Author(s):  
Eulogia Román ◽  
Ellen Miller ◽  
Allen Harmsen ◽  
James Wiley ◽  
Ulrich H. von Andrian ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Interferon Γ ◽  
T Cell Subsets ◽  
Effector Cells ◽  
Effector T Cell ◽  
Resting Cell ◽  
Cell Divisions ◽  
And Function ◽  
Secondary Lymphoid Organs ◽  
Draining Lymph Nodes

The immune response of naive CD4 T cells to influenza virus is initiated in the draining lymph nodes and spleen, and only after effectors are generated do antigen-specific cells migrate to the lung which is the site of infection. The effector cells generated in secondary organs appear as multiple subsets which are a heterogeneous continuum of cells in terms of number of cell divisions, phenotype and function. The effector cells that migrate to the lung constitute the more differentiated of the total responding population, characterized by many cell divisions, loss of CD62L, down-regulation of CCR7, stable expression of CD44 and CD49d, and transient expression of CCR5 and CD25. These cells also secrete high levels of interferon γ and reduced levels of interleukin 2 relative to those in the secondary lymphoid organs. The response declines rapidly in parallel with viral clearance, but a spectrum of resting cell subsets reflecting the pattern at the peak of response is retained, suggesting that heterogeneous effector populations may give rise to corresponding memory populations. These results reveal a complex response, not an all-or-none one, which results in multiple effector phenotypes and implies that effector cells and the memory cells derived from them can display a broad spectrum of functional potentials.

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