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fibroblast treg

Anh Duc Truong, Yeojin Hong, Cong Thanh Hoang, Janggeun Lee, Yeong Ho Hong
Chicken interleukin 26 (ChIL-26), a member of the IL-10 family, is expressed in T cells and can induce expression of proinflammatory cytokines. We examined the response of signal transduction pathways to ChIL-26 stimulation in the chicken T (CU91), macrophage (HD11), and fibroblast (OU2) cell lines. ChIL-26 activated JAK2 and TYK2 phosphorylation, as well as activation of STAT1, STAT3, and SHP2 via tyrosine/serine residues. We also showed that ChIL-26 activates the phosphorylation of NF-κB1, TAK1, and MyD88 kinase, which are key regulators of NF-κB signaling pathways...
March 2, 2017: Developmental and Comparative Immunology
Vimal Ramjee, Deqiang Li, Lauren J Manderfield, Feiyan Liu, Kurt A Engleka, Haig Aghajanian, Christopher B Rodell, Wen Lu, Vivienne Ho, Tao Wang, Li Li, Anamika Singh, Dasan M Cibi, Jason A Burdick, Manvendra K Singh, Rajan Jain, Jonathan A Epstein
Ischemic heart disease resulting from myocardial infarction (MI) is the most prevalent form of heart disease in the United States. Post-MI cardiac remodeling is a multifaceted process that includes activation of fibroblasts and a complex immune response. T-regulatory cells (Tregs), a subset of CD4+ T cells, have been shown to suppress the innate and adaptive immune response and limit deleterious remodeling following myocardial injury. However, the mechanisms by which injured myocardium recruits suppressive immune cells remain largely unknown...
March 1, 2017: Journal of Clinical Investigation
Maria Antonella Laginestra, Claudio Tripodo, Claudio Agostinelli, Giovanna Motta, Sylvia Hartmann, Claudia Doring, Maura Rossi, Federica Melle, Maria Rosaria Sapienza, Valentina Tabanelli, Alessandro Pileri, Fabio Fuligni, Anna Gazzola, Claudia Mannu, Carlo Alberto Sagramoso, Silvia Lonardi, Luisa Lorenzi, Francesco Bacci, Elena Sabattini, Anita Borges, Ingrid Simonitsch-Klupp, Jose Cabecadas, Elias Campo, Juan Rosai, Martin-Leo Hansmann, Fabio Facchetti, Stefano Aldo Pileri
Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors (MTs) with variable clinical, morphologic and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared to other MTs, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other MTs and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n=1,289) between microdissected FDCs and fibroblasts...
January 27, 2017: Molecular Cancer Research: MCR
Carl D Richards
Chronic inflammation can be caused by adaptive immune responses in autoimmune and allergic conditions, driven by a T lymphocyte subset balance (TH1, TH2, Th17, Th22, and/or Treg) and skewed cellular profiles in an antigen-specific manner. However, several chronic inflammatory diseases have no clearly defined adaptive immune mechanisms that drive chronicity. These conditions include those that affect the lung such as nonatopic asthma or idiopathic pulmonary fibrosis comprising significant health problems. The remodeling of extracellular matrix (ECM) causes organ dysfunction, and it is largely generated by fibroblasts as the major cell controlling net ECM...
February 2017: Journal of Interferon & Cytokine Research
Qiu Xia, Fei Geng, Fang-Fang Zhang, Chen-Lu Liu, Ping Xu, Zhen-Zhen Lu, Yu Xie, Bo Sun, Hui Wu, Bin Yu, Wei Kong, Xiang-Hui Yu, Hai-Hong Zhang
Cyclophosphamide (CY) is a DNA alkylating agent, which is widely used with other chemotherapy drugs in the treatment of various types of cancer. It can be used not only as a chemotherapeutic but also as an immunomodulatory agent to inhibit IL-10 expression and T regulatory cells (Tregs). Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts in the tumor microenvironment. Immunotherapy based on FAPα, as a tumor stromal antigen, typically induces specific immune response targeting the tumor microenvironment...
February 2017: Immunopharmacology and Immunotoxicology
Takahiro Tsuchikawa, Shintaro Takeuchi, Toru Nakamura, Toshiaki Shichinohe, Satoshi Hirano
A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells...
November 15, 2016: World Journal of Gastrointestinal Oncology
Meirong Huo, Yan Zhao, Andrew Benson Satterlee, Yuhua Wang, Ying Xu, Leaf Huang
Development of an effective treatment against advanced tumors remains a major challenge for cancer immunotherapy. We have previously developed a potent mannose-modified lipid calcium phosphate (LCP) nanoparticle (NP)-based Trp2 vaccine for melanoma therapy, but because this vaccine can induce a potent anti-tumor immune response only during the early stages of melanoma, poor tumor growth inhibition has been observed in more advanced melanoma models, likely due to the development of an immune-suppressive tumor microenvironment (TME)...
January 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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...
November 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...
April 23, 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...
February 22, 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...
December 10, 2015: Arthritis Research & Therapy
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