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fibroblast treg

Jason R Pitarresi, Xin Liu, Sudarshana M Sharma, Maria C Cuitiño, Raleigh D Kladney, Thomas A Mace, Sydney Donohue, Sunayana G Nayak, Chunjing Qu, James Lee, Sarah A Woelke, Stefan Trela, Kyle LaPak, Lianbo Yu, Joseph McElroy, Thomas J Rosol, Reena Shakya, Thomas Ludwig, Gregory B Lesinski, Soledad A Fernandez, Stephen F Konieczny, Gustavo Leone, Jinghai Wu, Michael C Ostrowski
Preclinical studies have suggested that the pancreatic tumor microenvironment both inhibits and promotes tumor development and growth. Here we establish the role of stromal fibroblasts during acinar-to-ductal metaplasia (ADM), an initiating event in pancreatic cancer formation. The transcription factor V-Ets avian erythroblastosis virus E26 oncogene homolog 2 (ETS2) was elevated in smooth muscle actin-positive fibroblasts in the stroma of pancreatic ductal adenocarcinoma (PDAC) patient tissue samples relative to normal pancreatic controls...
September 2016: Neoplasia: An International Journal for Oncology Research
Yu-Ling Wang, Ju-Mei Gao, Li-Zhi Xing
Excessive inflammation contributes greatly to the pathogenesis and development of rheumatoid arthritis (RA). Oroxylin A (OA) is a natural anti-inflammatory flavonoid compound. In this study, we investigated the effects of OA on collagen-induced arthritis (CIA) and human RA fibroblast-like synoviocytes (FLS). CIA was induced in DBA/1 mice and mice were intraperitoneally treated with OA (10mg/kg) for 10days. Arthritis severity was evaluated every day and the histopathologic examination of joints was done. Serum levels of anti-collagen II antibodies (anti-CII Abs) and cytokines were determined by ELISA...
September 16, 2016: International Immunopharmacology
Takuya Matsumoto, Nobunori Takahashi, Toshihisa Kojima, Yutaka Yoshioka, Jun Ishikawa, Koichi Furukawa, Kenji Ono, Makoto Sawada, Naoki Ishiguro, Akihito Yamamoto
BACKGROUND: The aim of this study was to assess the effects of soluble sialic acid-binding immunoglobulin-type lectin (sSiglec)-9 on joint inflammation and destruction in a murine collagen-induced arthritis (CIA) model and in monolayer cultures of murine macrophages (RAW264.7 cells and peritoneal macrophages) and fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis. METHODS: DBA/1J mice were immunized with type II collagen. Effects of sSiglec-9 were evaluated using a physiologic arthritis score, histological analysis, serum tumor necrosis factor (TNF)-α concentration, and the proportion of forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells...
2016: Arthritis Research & Therapy
Wei Guo, Dongmei Yu, Xin Wang, Cheng Luo, Yucong Chen, Wen Lei, Chen Wang, Yaoyao Ge, Wenyao Xue, Qiqi Tian, Xiangdong Gao, Wenbing Yao
IL-23 is an important cytokine to regulate Th17 cell differentiation and promote the proliferation of inflammatory cells in Th17-mediated autoimmune diseases. The collagen-induced arthritis (CIA) in rat is a model of rheumatoid arthritis characterized by pronounced inflammatory auto-responses from B and T cells, especially Th17 cells in lesions. In the present study, we used rhIL23R-CHR to block the IL-23 signaling pathway to probe the importance of IL-23 in misbalancing the ratio of Th17/Th9/Treg cells in CIA rats...
May 31, 2016: Oncotarget
Jia Ng, Kim Hynes, Gregory White, Kisha Nandini Sivanathan, Kate Vandyke, P Mark Bartold, Stan Gronthos
MSC-like populations derived from induced pluripotent stem cells (iPSC-MSC) serve as an alternative stem cell source due to their high proliferative capacity. In this study, we assessed the immunomodulatory potential of iPSC-MSC generated from periodontal ligament (PDL) and gingival (GF) tissue. The iPSC-MSC lines exhibited a similar level of suppression of mitogen-stimulated peripheral blood mononuclear cells (PBMNC) proliferation compared to their respective parental fibroblast populations in vitro. Moreover, iPSC-MSC demonstrated the ability to suppress T-cells effector cells, Th1/Th2/Th17 populations, and increase levels of Treg cells...
May 11, 2016: Journal of Cellular Biochemistry
Ming Liu, Xiansheng Zeng, Junli Wang, Zhiping Fu, Jinsong Wang, Muyun Liu, Dunqiang Ren, Baodan Yu, Lixia Zheng, Xiang Hu, Wei Shi, Jun Xu
BACKGROUND: Interstitial pneumonia in connective tissue diseases (CTD-IP) featuring inflammation and fibrosis is a leading cause of death in CTD-IP patients. The related autoimmune lung injury and disturbed self-healing process make conventional anti-inflammatory drugs ineffective. Equipped with unique immunoregulatory and regenerative properties, mesenchymal stem cells (MSCs) may represent a promising therapeutic agent in CTD-IP. In this study, we aim to define the immunopathology involved in pulmonary exacerbation during autoimmunity and to determine the potential of MSCs in correcting these disorders...
2016: Stem Cell Research & Therapy
Eun Kyung Kim, Seung Hoon Lee, Joo Yeon Jhun, Jae Kyeong Byun, Jeong Hee Jeong, Seon-Young Lee, Jae Kyung Kim, Jong Young Choi, Mi-La Cho
Obesity and its associated metabolic disorders are related to the onset of fatty liver and the balance of white adipose tissue (WAT) and brown adipose tissue (BAT). We hypothesized that metformin, an effective pharmacological treatment for type 2 diabetes, would inhibit white adipogenesis, fatty liver, and metabolic dysfunction. Metformin was treated daily for 14 weeks in a high-fat dieting C57BL/6J mice. Serum biomarkers were analyzed and protein level was assessed using confocal staining or flow cytometry...
2016: Mediators of Inflammation
J-T Cheng, Y-N Deng, H-M Yi, G-Y Wang, B-S Fu, W-J Chen, W Liu, Y Tai, Y-W Peng, Q Zhang
Although carcinoma-associated fibroblasts (CAFs) in tumor microenvironments have a critical role in immune cell modulation, their effects on the generation of regulatory dendritic cells (DCs) are still unclear. In this study, we initially show that CAFs derived from hepatocellular carcinoma (HCC) tumors facilitate the generation of regulatory DCs, which are characterized by low expression of costimulatory molecules, high suppressive cytokines production and enhanced regulation of immune responses, including T-cell proliferation impairment and promotion of regulatory T-cell (Treg) expansion via indoleamine 2,3-dioxygenase (IDO) upregulation...
2016: Oncogenesis
Wojciech Jóźwicki, Anna A Brożyna, Jerzy Siekiera, Andrzej T Slominski
Tumor cells communicate with stromal cells, including cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), to form microenvironment inhibiting immune responses. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) stimulate immune tolerance and facilitate tumor progression. We analyzed the changes in Treg frequencies assessed using flow cytometry in the peripheral blood of patients with urothelial bladder cancer before and after tumor-removal. Changes in Treg frequency were investigated in relation to clinicopathomorphological indicators of tumor malignancy and expression of RCAS1 on CAFs and TAMs...
March 8, 2016: Oncotarget
Yun Zhang, Reza B Jalili, Ruhangiz T Kilani, Sanam Salimi Elizei, Ali Farrokhi, Mohsen Khosravi-Maharlooei, Garth L Warnock, Ziliang Ao, Lucy Marzban, Aziz Ghahary
Indoleamine 2,3-dioxygenase (IDO) induces immunological tolerance in physiological and pathological conditions. Therefore, we used dermal fibroblasts with stable IDO expression as a cell therapy to: (i) Investigate the factors determining the efficacy of this cell therapy for autoimmune diabetes in non-obese diabetic (NOD) mice; (ii) Scrutinize the potential immunological mechanisms. Newly diabetic NOD mice were randomly injected with either 10 × 10(6) (10M) or 15 × 10(6) (15M) IDO-expressing dermal fibroblasts...
September 2016: Journal of Cellular Physiology
Hongfang Ding, Hui Zhang, Huifang Ding, Dong Li, Xinhao Yi, Xiaoxu Ma, Ruijuan Li, Mei Huang, Xiuli Ju
Hypoxic-ischemic brain damage (HIBD) is a common cause of infant death. The purpose of our research was to explore the immunoregulatory mechanism of placenta-derived mesenchymal stem cells (PD-MSCs) in HIBD treatment. Seven-day-old rat pups were randomly divided into HIBD, PD-MSC, fibroblast, and control groups. Forty-eight hours after HIBD induction, cells at a density of 5 × 104 cells/10 µl were injected into the cerebral tissue in the PD-MSC and fibroblast groups. The TNF-α, interleukin- 17 (IL-17), interferon-γ (IFN-γ), and IL-10 levels were detected through quantitative real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA)...
December 28, 2015: Cellular & Molecular Immunology
Andras Perl
Mechanistic target of rapamycin (mTOR, also known as mammalian target of rapamycin) is a ubiquitous serine/threonine kinase that regulates cell growth, proliferation and survival. These effects are cell-type-specific, and are elicited in response to stimulation by growth factors, hormones and cytokines, as well as to internal and external metabolic cues. Rapamycin was initially developed as an inhibitor of T-cell proliferation and allograft rejection in the organ transplant setting. Subsequently, its molecular target (mTOR) was identified as a component of two interacting complexes, mTORC1 and mTORC2, that regulate T-cell lineage specification and macrophage differentiation...
March 2016: Nature Reviews. Rheumatology
Alba Llop-Guevara, Mónica Porras, Carla Cendón, Irene Di Ceglie, Francesco Siracusa, Federica Madarena, Vagelis Rinotas, Lluís Gómez, Peter L van Lent, Eleni Douni, Hyun Dong Chang, Thomas Kamradt, Juan Román
INTRODUCTION: Despite the broad spectrum of antirheumatic drugs, RA is still not well controlled in up to 30-50 % of patients. Inhibition of JAK kinases by means of the pan-JAK inhibitor tofacitinib has demonstrated to be effective even in difficult-to-treat patients. Here, we discuss whether the efficacy of JAK inhibition can be improved by simultaneously inhibiting SYK kinase, since both kinases mediate complementary and non-redundant pathways in RA. METHODS: Efficacy of dual JAK + SYK inhibition with selective small molecule inhibitors was evaluated in chronic G6PI-induced arthritis, a non-self-remitting and destructive arthritis model in mice...
2015: Arthritis Research & Therapy
Lin-Ying Chen, Julia Y S Tsang, Yun-Bi Ni, Siu-Ki Chan, Kui-Fat Chan, Sheng Zhang, Gary M Tse
AIMS: Sclerosing lymphocytic lobulitis (SLL) of the breast is characterised by lymphocytic lobulitis, ductitis, vasculitis and dense keloidal fibrosis with epithelioid fibroblasts. However, the subsets of the infiltrating lymphocytes and their contribution to disease progression have not been fully explored. METHODS: CD20, CD3, CD4, CD8 and regulatory T (Treg) lymphocytes were evaluated in the epithelial and vascular areas in SLL. The relationship between the lymphocyte subset in different regions and the degree of inflammation was analysed...
June 2016: Journal of Clinical Pathology
Ethan Rothschild, Debabrata Banerjee
This review combines the recent research on the subject of tumor immunology and methods of correcting the immune system's reaction to the tumor microenvironment while impeding the survival and growth of tumor cells, with a focus on breast cancer. Induction of hypoxia-inducible genes in the microenvironment leads to lowering of its pH. This impedes the adaptive immune response and acts to recruit cells of the immune system, which suppress the immune response. Regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs), and their derivatives coordinate an anti-autoimmunity response and a healing response in concert with tumor-secreted cytokines, enzymes, and antigens...
2015: Breast Cancer: Basic and Clinical Research
Sin Kim, Mi Kyung Park, Hak Sun Yu
In Trichinella spiralis infection, type 2 helper T (Th2) cell-related and regulatory T (Treg) cell-related immune responses are the most important immune events. In order to clarify which Toll-like receptors (TLRs) are closely associated with these responses, we analyzed the expression of mouse TLR genes in the small intestine and muscle tissue during T. spiralis infection. In addition, the expression of several chemokine- and cytokine-encoding genes, which are related to Th2 and Treg cell mediated immune responses, were analyzed in mouse embryonic fibroblasts (MEFs) isolated from myeloid differentiation factor 88 (MyD88)/TIR-associated proteins (TIRAP) and Toll receptor-associated activator of interferons (TRIF) adapter protein deficient and wild type (WT) mice...
August 2015: Korean Journal of Parasitology
Yan Zhao, Meirong Huo, Zhenghong Xu, Yuhua Wang, Leaf Huang
Lipid-calcium-phosphate nanoparticle (NP) delivery of Trp2 peptide vaccine is one of the most effective vaccine strategies against melanoma. However, due to the immunosuppressive microenvironment in the tumor, the achievement of potent immune responses remains a major challenge. NP delivery systems provide an opportunity to deliver chemotherapy agent to modulate the tumor microenvironment (TME) and improve the vaccine activity. Anti-inflammatory triterpenoid methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is a broad spectrum inhibitor of several signaling pathways that are important in both cancer cells and cells in the TME...
November 2015: Biomaterials
Shigeki Katoh, Masaki Ikeda, Hiroki Shimizu, Masaaki Abe, Yoshihiro Ohue, Keiji Mouri, Yoshihiro Kobashi, Mikio Oka
PURPOSE: Galectin-9 (Gal-9) is a β-galactoside-binding protein that exhibits various biological reactions, such as chemoattraction, cell aggregation, and apoptosis. Recent studies demonstrated that Gal-9 has a role as an immunomodulator in excessive immunological reactions by expanded regulatory T cells (Tregs). We examined the role of Gal-9 in the pathogenesis of one of the major idiopathic interstitial pneumonias, cryptogenic organizing pneumonia (COP) as compared with idiopathic pulmonary fibrosis (IPF)...
October 2015: Lung
Sharee A Basdeo, Barry Moran, Deborah Cluxton, Mary Canavan, Jennifer McCormick, Mary Connolly, Carl Orr, Kingston H G Mills, Douglas J Veale, Ursula Fearon, Jean M Fletcher
In autoimmune diseases such as rheumatoid arthritis (RA), regulatory T cells (Tregs) fail to constrain autoimmune inflammation; however, the reasons for this are unclear. We investigated T cell regulation in the RA joint. Tregs from RA synovial fluid suppressed autologous responder T cells; however, when compared with Tregs from healthy control peripheral blood, they were significantly less suppressive. Despite their reduced suppressive activity, Tregs in the RA joint were highly proliferative and expressed FOXP3, CD39, and CTLA-4, which are markers of functional Tregs...
July 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Victoria Barygina, Matteo Becatti, Torello Lotti, Silvia Moretti, Niccolò Taddei, Claudia Fiorillo
BACKGROUND: Vitiligo is a systemic dermatological disorder characterized by the loss of skin pigmentation due to melanocyte injury or aberrant functioning. Recent data underline its multifactorial etiology with significant involvement of autoimmune and redox alterations. The major role in vitiligo cellular immunity is displayed by augmented Th1 and Th17 and suppressed TREGs and Th2 lymphocyte populations. Our previous studies indicate a marked redox imbalance in perilesional ("PL", i...
August 2015: Journal of Dermatological Science
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