HSP Reactive T Cells are Anti-Inflammatory and Disease Suppressive in Arthritic Diseases

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

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Probiotic supplementation reduces inflammatory profiles but does not prevent oral immune perturbations during SIV infection

Scientific Reports ◽

10.1038/s41598-021-93918-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rhianna Jones ◽

Kyle Kroll ◽

Courtney Broedlow ◽

Luca Schifanella ◽

Scott Smith ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cd4 T Cells ◽

Cell Activation ◽

Rhesus Macaques ◽

Oral Microbiome ◽

Probiotic Supplementation ◽

Siv Infection ◽

Anti Inflammatory

AbstractHIV/SIV infections lead to massive loss of mucosal CD4 + T cells and breakdown of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one of the most understudied mucosal environments, the oral cavity, during HIV-induced immunosuppression results in significant microbial and neoplastic co-morbidities and contributes to and predicts distal disease complications. In this study we evaluated the effects of oral probiotic supplementation (PBX), which can stimulate and augment inflammatory or anti-inflammatory pathways, on early SIV infection of rhesus macaques. Our study revealed that similar to the GI mucosae, oral CD4 + T cells were rapidly depleted, and as one of the first comprehensive analyses of the oral microflora in SIV infection, we also observed significant modulation among two genera, Porphyromonas and Actinobacillus, early after infection. Interestingly, although PBX therapy did not substantially protect against oral dysbiosis or ameliorate cell loss, it did somewhat dampen inflammation and T cell activation. Collectively, these data provide one of the most comprehensive evaluations of SIV-induced changes in oral microbiome and CD4 + T cell populations, and also suggest that oral PBX may have some anti-inflammatory properties in lentivirus infections.

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Chloroquine Protects Human Corneal Epithelial Cells from Desiccation Stress Induced Inflammation without Altering the Autophagy Flux

BioMed Research International ◽

10.1155/2018/7627329 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 8

Author(s):

Shivapriya Shivakumar ◽

Trailokyanath Panigrahi ◽

Rohit Shetty ◽

Murali Subramani ◽

Arkasubhra Ghosh ◽

...

Keyword(s):

T Cells ◽

Dry Eye ◽

Desiccation Stress ◽

Autophagy Flux ◽

Corneal Epithelial ◽

Corneal Fibroblasts ◽

Gene And Protein Expression ◽

Human Corneal Epithelial Cells ◽

Anti Inflammatory

Dry eye disease (DED) is a multifactorial ocular surface disorder affecting millions of individuals worldwide. Inflammation has been associated with dry eye and anti-inflammatory drugs are now being targeted as the alternate therapeutic approach for dry eye condition. In this study, we have explored the anti-inflammatory and autophagy modulating effect of chloroquine (CQ) in human corneal epithelial and human corneal fibroblasts cells exposed to desiccation stress, (anin-vitromodel for DED). Gene and protein expression profiling of inflammatory and autophagy related molecular factors were analyzed in HCE-T and primary HCF cells exposed to desiccation stress with and without CQ treatment. HCE-T and HCF cells exposed to desiccation stress exhibited increased levels of activated p65, TNF-α, MCP-1, MMP-9, and IL-6. Further, treatment with CQ decreased the levels of active p65, TNF-α, MCP-1, and MMP-9 in cells underdesiccation stress. Increased levels of LC3B and LAMP1 markers in HCE-T cells exposed to desiccation stress suggest activation of autophagy and the addition of CQ did not alter these levels. Changes in the phosphorylation levels of MAPKinase and mTOR pathway proteins were found in HCE-T cells under desiccation stress with or without CQ treatment. Taken together, the data suggests that HCE-T cells under desiccation stress showed NFκB mediated inflammation, which was rescued through the anti-inflammatory effect of CQ without altering the autophagy flux. Therefore, CQ may be used as an alternate therapeutic management for dry eye condition.

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In vivo inhibition of Nuclear Factor of Activated T‐cells (NFAT) results in enhanced levels of anti‐inflammatory IL‐10 in the retina of diabetic mice

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.777.17 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Anna V Zetterqvist ◽

Jenny Nilsson‐Öhman ◽

Olga Kotova ◽

Lisa M Nilsson‐Berglund ◽

Sergio Frutos Garcia ◽

...

Keyword(s):

T Cells ◽

Nuclear Factor ◽

Diabetic Mice ◽

Activated T Cells ◽

Anti Inflammatory

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Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on Colitis Through PGE2-Mediated T-Cell Modulation

Cell Transplantation ◽

10.1177/0963689718780304 ◽

2018 ◽

Vol 27 (9) ◽

pp. 1352-1367 ◽

Cited By ~ 15

Author(s):

Fu Yuan Yang ◽

Rui Chen ◽

Xiaohu Zhang ◽

Biao Huang ◽

Lai Ling Tsang ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Therapeutic Effect ◽

T Cell Activation ◽

Activity Index ◽

Intraperitoneal Administration ◽

The Body ◽

Human Umbilical Cord ◽

Therapeutic Effects ◽

Anti Inflammatory

Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration. In this study, we evaluated the effect of preconditioning on the immunoregulatory function of human umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating IBD. Our results show that intraperitoneal administration of deconditioned hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological colitis score and destruction of the epithelial barrier, and increases the body weight recovery more intensively than that of un-manipulated hUCMSCs. In addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction of the ERK pathway during the early stage of IBD development. In vitro co-culture studies indicate that De-hUCMSCs suppress T-cell proliferation and activation more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of inflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is significantly increased in De-hUCMSCs, the suppression of which dramatically abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we have demonstrated that preconditioning enhances the immunosuppressive and therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.

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Protective effect of Lactobacillus reuteri DSM 17938 against experimental necrotizing enterocolitis is mediated by Toll-like receptor 2

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00084.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. G231-G240 ◽

Cited By ~ 13

Author(s):

Thomas K. Hoang ◽

Baokun He ◽

Ting Wang ◽

Dat Q. Tran ◽

J. Marc Rhoads ◽

...

Keyword(s):

T Cells ◽

Necrotizing Enterocolitis ◽

Immune Modulation ◽

Lactobacillus Reuteri ◽

Inflammatory Responses ◽

Cow Milk ◽

Toll Like Receptor ◽

Toll Like Receptor 2 ◽

Anti Inflammatory

Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to reduce the incidence and severity of necrotizing enterocolitis (NEC). It is unclear if preventing NEC by LR 17938 is mediated by Toll-like receptor 2 (TLR2), which is known to mediate proinflammatory responses to bacterial cell wall components. NEC was induced in newborn TLR2−/− or wild-type (WT) mice by the combination of gavage-feeding cow milk-based formula and exposure to hypoxia and cold stress. Treatment groups were administered formula supplemented with LR 17938 or placebo (deMan-Rogosa-Sharpe media). We observed that LR 17938 significantly reduced the incidence of NEC and reduced the percentage of activated effector CD4+T cells, while increasing Foxp3+ regulatory T cells in the intestinal mucosa of WT mice with NEC, but not in TLR2−/− mice. Dendritic cell (DC) activation by LR 17938 was mediated by TLR2. The percentage of tolerogenic DC in the intestine of WT mice was increased by LR 17938 treatment during NEC, a finding not observed in TLR2−/− mice. Furthermore, gut levels of proinflammatory cytokines IL-1β and IFN-γ were decreased after treatment with LR 17938 in WT mice but not in TLR2−/− mice. In conclusion, the combined in vivo and in vitro findings suggest that TLR2 receptors are involved in DC recognition and DC-priming of T cells to protect against NEC after oral administration of LR 17938. Our studies further clarify a major mechanism of probiotic LR 17938 action in preventing NEC by showing that neonatal immune modulation of LR 17938 is mediated by a mechanism requiring TLR2. NEW & NOTEWORTHY Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to protect against necrotizing enterocolitis (NEC) in neonates and in neonatal animal models. The role of Toll-like receptor 2 (TLR2) as a sensor for gram-positive probiotics, activating downstream anti-inflammatory responses is unclear. Our current studies examined TLR2 −/− mice subjected to experimental NEC and demonstrated that the anti-inflammatory effects of LR 17938 are mediated via a mechanism requiring TLR2.

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Immunopathogenesis of Acute Kidney Injury

Toxicologic Pathology ◽

10.1177/0192623318799976 ◽

2018 ◽

Vol 46 (8) ◽

pp. 930-943 ◽

Cited By ~ 11

Author(s):

Zaher A. Radi

Keyword(s):

Acute Kidney Injury ◽

T Cells ◽

Kidney Tissue ◽

Kidney Injury ◽

Drug Induced ◽

Inflammatory Damage ◽

Anti Inflammatory ◽

Renal Tubular ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

Pathophysiologically, the classification of acute kidney injury (AKI) can be divided into three categories: (1) prerenal, (2) intrinsic, and (3) postrenal. Emerging evidence supports the involvement of renal tubular epithelial cells and the innate and adaptive arms of the immune system in the pathogenesis of intrinsic AKI. Pro-inflammatory damage-associated molecular patterns, pathogen-associated molecular patterns, hypoxia inducible factors, toll-like receptors, complement system, oxidative stress, adhesion molecules, cell death, resident renal dendritic cells, neutrophils, T and B lymphocytes, macrophages, natural killer T cells, cytokines, and secreted chemokines contribute to the immunopathogenesis of AKI. However, other immune cells and pathways such as M2 macrophages, regulatory T cells, progranulin, and autophagy exhibit anti-inflammatory properties and facilitate kidney tissue repair after AKI. Thus, therapies for AKI include agents such as anti-inflammatory (e.g., recombinant alkaline phosphatase), antioxidants (iron chelators), and apoptosis inhibitors. In preclinical toxicity studies, drug-induced kidney injury can be seen after exposure to a nephrotoxicant test article due to immune mechanisms and dysregulation of innate, and/or adaptive cellular immunity. The focus of this review will be on intrinsic AKI, as it relates to the immune and renal systems cross talks focusing on the cellular and pathophysiologic mechanisms of AKI.

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Abstract WMP73: Peripheral T Cells From MCAO Mice Contribute to Microglial Polarization

Stroke ◽

10.1161/str.48.suppl_1.wmp73 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Dan Ye ◽

Yun Xu

Keyword(s):

T Cells ◽

Th17 Cells ◽

Inflammatory Cells ◽

Treg Cells ◽

Experimental Stroke ◽

Dual Roles ◽

Microglial Polarization ◽

Peripheral T Cells ◽

Anti Inflammatory

Both resident microglia and infiltrated peripheral T cells have been proved to play important roles in the pathology of stroke. It is well accepted that activated microglia exert dual roles, including pro-inflammatory (M1) and anti-inflammatory (M2) functions. However, the mechanism regulating microglial polarization remains elusive. T cells are recruited into the ischemic area within 24 h after stroke, which also exhibit pro-inflammatory (Th1, Th17) and anti-inflammatory (Th2, Treg) functions. The interaction between microglia and T cells after stroke is barely understood, which may be served as modifiers of pathobiology in stroke. Here we described the role of T cells in the microglial polarization in mouse experimental stroke. We isolated T cells from spleens of MCAO mice at 24 h and 72 h, respectively, and then added to cultured microglia for 24 h. Our results indicated that splenic T cells obtained at 24 h after MCAO selectively promoted microglia polarize to a pro-inflammatory (M1) state, while T cells obtained at 72 h, favored microglia polarize to an anti-inflammatory (M2) state. The results of flow cytometry showed that Th1 and Th17 cells increased at 24 h after MCAO while Th2 and Treg cells increased at 72 h after MCAO. This study implicates that distinct subtypes of T cells contribute differentially to microglial polarization after stroke onset. Therefore, treatments aiming at modulating the ratios of T cells to anti-inflammatory cells have the potential to induce microglial polarize to M2 phenotype and improve the outcome of ischemic stroke.

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