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https://www.readbyqxmd.com/read/29722898/lw106-a-novel-inhibitor-of-ido1-suppresses-tumor-progression-by-limiting-stroma-immune-crosstalk-and-cancer-stem-cell-enrichment-in-the-tumor-microenvironment
#1
Rong Fu, Yi-Wei Zhang, Hong-Mei Li, Wen-Cong Lv, Li Zhao, Qing-Long Guo, Tao Lu, Stephen J Weiss, Zhi-Yu Li, Zhao-Qiu Wu
BACKGROUND AND PURPOSE: Indoleamine 2,3-dioxygenase 1 (IDO1) is emerging as an important new therapeutic target for treatment of malignant tumors characterized by dysregulated tryptophan metabolism. However, the antitumor efficacy of existing small-molecule inhibitors of IDO1 is still unsatisfactory and the underlying mechanism remains largely undefined. Hence, we discovered a novel potent small-molecule inhibitor of IDO1, LW106, and studied its antitumor effects and the underlying mechanisms in two Tumor models...
May 3, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29690905/resolution-of-bleomycin-induced-murine-pulmonary-fibrosis-via-a-splenic-lymphocyte-subpopulation
#2
Koichiro Kamio, Arata Azuma, Kuniko Matsuda, Jiro Usuki, Minoru Inomata, Akemi Morinaga, Takeru Kashiwada, Nobuhiko Nishijima, Shioto Itakura, Nariaki Kokuho, Kenichiro Atsumi, Hiroki Hayashi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality, and the pathogenesis of the disease is still incompletely understood. Although lymphocytes, especially CD4+ CD25+ FoxP3+ regulatory T cells (Tregs), have been implicated in the development of IPF, contradictory results have been reported regarding the contribution of Tregs to fibrosis both in animals and humans. The aim of this study was to investigate whether a specific T cell subset has therapeutic potential in inhibiting bleomycin (BLM)-induced murine pulmonary fibrosis...
April 24, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29415756/fli1-haploinsufficient-dermal-fibroblasts-promote-skin-localized-transdifferentiation-of-th2-like-regulatory-t-cells
#3
Ryosuke Saigusa, Yoshihide Asano, Takashi Taniguchi, Megumi Hirabayashi, Kouki Nakamura, Shunsuke Miura, Takashi Yamashita, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Ayumi Yoshizaki, Maria Trojanowska, Shinichi Sato
BACKGROUND: Friend leukemia virus integration 1 (Fli1) deficiency, a predisposing factor of systemic sclerosis (SSc), induces SSc-like phenotypes in various cell types. A recent study demonstrated the transdifferentiation of T helper type 2 cell (Th2)-like regulatory T cells (Tregs) in SSc lesional skin through interleukin (IL)-33 produced by fibroblasts. Therefore, we investigated the role of Fli1 deficiency in dermal fibroblast-mediated transdifferentiation of Tregs. METHODS: Cytokine expression was assessed in Tregs by flow cytometry and in skin samples and cultivated cells by immunostaining, immunoblotting, and/or qRT-PCR...
February 7, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29367090/inhibition-of-nf-%C3%AE%C2%BAb-pathway-in-fibroblast-like-synoviocytes-by-%C3%AE-mangostin-implicated-in-protective-effects-on-joints-in-rats-suffering-from-adjuvant-induced-arthritis
#4
Jian Zuo, Qin Yin, Yu-Wei Wang, Yan Li, Lin-Ming Lu, Zhan-Gang Xiao, Guo-Dong Wang, Jia-Jie Luan
α-Mangostin (MG) is a bioactive compound isolated from mangosteen. This study was aimed to investigate effects of MG on adjuvant-induced arthritis (AA) in rats and decipher the underlying mechanisms. Clinical severity of AA was evaluated by paw oedema, arthritis score, and hematological parameters. Digital radiography (DR) and histological examinations were employed to assess joints destructions. Immune functions were evaluated by T cell subsets distribution. Effects on NF-κB pathway were investigated by immunohistochemical, western-blot and immunofluorescence methods both in vivo and vitro...
March 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29301364/immune-evasion-in-pancreatic-cancer-from-mechanisms-to-therapy
#5
REVIEW
Neus Martinez-Bosch, Judith Vinaixa, Pilar Navarro
Pancreatic ductal adenocarcinoma (PDA), the most frequent type of pancreatic cancer, remains one of the most challenging problems for the biomedical and clinical fields, with abysmal survival rates and poor therapy efficiency. Desmoplasia, which is abundant in PDA, can be blamed for much of the mechanisms behind poor drug performance, as it is the main source of the cytokines and chemokines that orchestrate rapid and silent tumor progression to allow tumor cells to be isolated into an extensive fibrotic reaction, which results in inefficient drug delivery...
January 3, 2018: Cancers
https://www.readbyqxmd.com/read/29273462/fibroblast-activation-proteins-%C3%AE-suppress-tumor-immunity-by-regulating-t-cells-and-tumor-associated-macrophages
#6
Chun Mei Hou, Xue Mei Qu, Jian Zhang, Ting Ting Ding, Wei Han, Guang Chuan Ji, Zhao Hua Zhong, He Chen, FengMin Zhang
Fibroblast activation protein-α (FAPα) is a type-II cell-surface-bound integral transmembrane serine protease and selectively overexpressed by tumor-associated stromal fibroblasts (TAFs), which are the main components in the tumor microenvironment, in >90% of malignant epithelial carcinomas. FAPα regulates the immunosuppression of tumor cells in the tumor microenvironment. Regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are the major immunosuppressive cells in the tumor microenvironment...
February 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29247993/interleukin-33-il-33-a-nuclear-cytokine-from-the-il-1-family
#7
REVIEW
Corinne Cayrol, Jean-Philippe Girard
Interleukin-33 (IL-33) is a tissue-derived nuclear cytokine from the IL-1 family abundantly expressed in endothelial cells, epithelial cells and fibroblast-like cells, both during homeostasis and inflammation. It functions as an alarm signal (alarmin) released upon cell injury or tissue damage to alert immune cells expressing the ST2 receptor (IL-1RL1). The major targets of IL-33 in vivo are tissue-resident immune cells such as mast cells, group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs)...
January 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29167008/-new-progress-in-the-relationship-between-immune-cells-pd-1-%C3%A2-in-tumor-microenvironment-and-the-efficacy-of-egfr-tkis
#8
Shiyang Yuan, Hui Xu, Junping Xie
In recent years, targeted therapy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) is the leading treatment modality for patients with advanced non-small cell lung cancer (NSCLC) and EGFR gene mutation. However, with the prolongation of the medication time, most of the patients appeared drug resistance. Tumor microenvironment is the internal environment for the survival and development of tumor cells. The immune response which mediated by immune cells, like regulatory T (Treg), dendritic cells, macrophages, fibroblasts, etc...
November 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29155098/orai1-mutations-abolishing-store-operated-ca-2-entry-cause-anhidrotic-ectodermal-dysplasia-with-immunodeficiency
#9
Jayson Lian, Mario Cuk, Sascha Kahlfuss, Lina Kozhaya, Martin Vaeth, Frédéric Rieux-Laucat, Capucine Picard, Melina J Benson, Antonia Jakovcevic, Karmen Bilic, Iva Martinac, Peter Stathopulos, Imre Kacskovics, Thomas Vraetz, Carsten Speckmann, Stephan Ehl, Thomas Issekutz, Derya Unutmaz, Stefan Feske
BACKGROUND: Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ channels is an essential signaling pathway in many cell types. Ca2+ release-activated Ca2+ channels are formed by ORAI1, ORAI2, and ORAI3 proteins and activated by stromal interaction molecule (STIM) 1 and STIM2. Mutations in the ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and nonimmunologic symptoms. OBJECTIVE: We performed molecular and immunologic analysis of patients with CID, anhidrosis, and ectodermal dysplasia of unknown etiology...
November 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29152078/cd163-as-a-novel-target-gene-of-stat3-is-a-potential-therapeutic-target-for-gastric-cancer
#10
Zhenguo Cheng, Danhua Zhang, Baocheng Gong, Pengliang Wang, Funan Liu
CD163 is a member of the scavenger receptor cysteine-rich superfamily, and has been widely used to identify M2 type macrophage. However, the expression of CD163 in gastric cancer and its regulatory mechanism are still unclear. Here we show that CD163 is elevated in gastric cancer tissues. High expression of CD163 is a potential indicator to evaluate the status of tumor associated macrophages (TAMs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and cancer associated fibroblasts (Cafs)...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29127315/human-gingiva-derived-mesenchymal-stem-cells-ameliorate-streptozoticin-induced-t1dm-in-mice-via-suppression-of-t-effector-cells-and-up-regulating-treg-subsets
#11
Wei Zhang, Li Zhou, Junlong Dang, Ximei Zhang, Julie Wang, Yanming Chen, Jichao Liang, Dongqing Li, Jilin Ma, Jia Yuan, Weiwen Chen, Homayoun H Zadeh, Nancy Olsen, Song Guo Zheng
There is yet no cure for type 1 diabetes (T1DM) so far. A significant body of evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) showed great potential in controlling T1DM. But there exists much difficulty in using BMSCs as a clinical therapy. We here test whether a new population of mesenchymal stem cells from human gingiva (GMSCs), which has many advantages over BMSCs, can delay or prevent progress of T1DM. GMSCs were adoptively transferred to multiple low-dose streptozotocin (STZ)-induced T1DM...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29106735/human-periodontal-ligament-fibroblasts-synthesize-c-reactive-protein-and-th-related-cytokines-in-response-to-interleukin-il-6-trans-signalling
#12
A Hernández-Caldera, R Vernal, R Paredes, P Veloso-Matta, J Astorga, M Hernández
AIM: To characterize the potential of human periodontal ligament fibroblasts (HPLF) to synthesize CRP and Th-related cytokines in response to IL-6 in periodontal health and apical inflammation. METHODOLOGY: Primary HPLF stimulated with IL-6, soluble(s) IL-6 receptor (R) and controls were assayed for CRP, Th1, Th2, Th17 and Treg-related cytokines by quantitative real-time PCR and ELISA, respectively. IL-6R mRNA expression and its soluble protein levels were screened in HPLF cultures, and ex vivo samples of healthy periodontal ligaments (n = 5) and apical lesions (n = 13)...
November 6, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28881756/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#13
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28833065/mesenteric-lymph-node-stromal-cell-derived-extracellular-vesicles-contribute-to-peripheral-de-novo-induction-of-foxp3-regulatory-t-cells
#14
Maria Pasztoi, Joern Pezoldt, Michael Beckstette, Christoph Lipps, Dagmar Wirth, Manfred Rohde, Krisztina Paloczi, Edit Iren Buzas, Jochen Huehn
Intestinal regulatory T cells (Tregs) are fundamental in peripheral tolerance toward commensals and food-borne antigens. Accordingly, gut-draining mesenteric lymph nodes (mLNs) represent a site of efficient peripheral de novo Treg induction when compared to skin-draining peripheral LNs (pLNs), and we had recently shown that LN stromal cells substantially contribute to this process. Here, we aimed to unravel the underlying molecular mechanisms and generated immortalized fibroblastic reticular cell lines (iFRCs) from mLNs and pLNs, allowing unlimited investigation of this rare stromal cell subset...
December 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28795730/role-of-garp-in-the-activation-of-latent-tgf-%C3%AE-1
#15
REVIEW
Julie Stockis, Olivier Dedobbeleer, Sophie Lucas
TGF-β1, 2 and 3 cytokines are involved in many cellular processes including cell proliferation, differentiation, migration and survival. Whereas TGF-β2 and 3 play important roles in embryonic development, TGF-β1 is mostly implicated in controlling immune responses after birth. The production of TGF-β1 is a tightly regulated process, occurring mostly at a post-translational level. Virtually all cells produce the latent, inactive form of TGF-β1. In latent TGF-β1, the mature TGF-β1 dimer is non-covalently associated to the Latency Associated Peptide, or LAP, which prevents binding to the TGF-β1 receptor...
September 26, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28758901/stromal-cell-cadherin-11-regulates-adipose-tissue-inflammation-and-diabetes
#16
Sook Kyung Chang, Ayano C Kohlgruber, Fumitaka Mizoguchi, Xavier Michelet, Benjamin J Wolf, Kevin Wei, Pui Y Lee, Lydia Lynch, Danielle Duquette, Victòria Ceperuelo-Mallafré, Alexander S Banks, Michael B Brenner
M2 macrophages, innate lymphoid type 2 cells (ILC2s), eosinophils, Tregs, and invariant NK T cells (iNKT cells) all help to control adipose tissue inflammation, while M1 macrophages, TNF, and other inflammatory cytokines drive inflammation and insulin resistance in obesity. Stromal cells regulate leukocyte responses in lymph nodes, but the role of stromal cells in adipose tissue inflammation is unknown. PDGFRα+ stromal cells are major producers of IL-33 in adipose tissue. Here, we show that mesenchymal cadherin-11 modulates stromal fibroblast function...
September 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28687373/il-33-and-the-intestine-the-good-the-bad-and-the-inflammatory
#17
REVIEW
Zerina Hodzic, Ellen Merrick Schill, Alexa M Bolock, Misty Good
Interleukin-33 (IL-33) is a member of the IL-1 cytokine family that has been widely studied since its discovery in 2005 for its dichotomous functions in homeostasis and inflammation. IL-33, along with its receptor suppression of tumorigenicity 2 (ST2), has been shown to modulate both the innate and adaptive immune system. Originally, the IL-33/ST2 signaling axis was studied in the context of inducing type 2 immune responses with the expression of ST2 by T helper 2 (TH 2) cells. However, the role of IL-33 is not limited to TH 2 responses...
December 2017: Cytokine
https://www.readbyqxmd.com/read/28673339/human-limbal-fibroblast-like-stem-cells-induce-immune-tolerance-in-autoreactive-t-lymphocytes-from-female-patients-with-hashimoto-s-thyroiditis
#18
Antonina Coppola, Laura Tomasello, Maria Pitrone, Salvatore Cillino, Pierina Richiusa, Giuseppe Pizzolanti, Carla Giordano
BACKGROUND: Due to their "natural immune privilege" and immunoregulatory properties human fibroblast-like limbal stem cells (f-LSCs) have acquired great interest as a potential tool for achieving immunotolerance. Hashimoto's thyroiditis (HT) is the most common thyroid autoimmune disease and cause of hypothyroidism. To date, conventional hormone replacement therapy and unspecific immunosuppressive regimens cannot provide a definitive cure for HT subjects. We explored the immunosuppressant potential of human f-LSCs on circulating lymphomonocytes (PBMCs) collected from healthy donors and female HT patients...
July 3, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28667560/cardiac-autoimmunity-myocarditis
#19
REVIEW
William Bracamonte-Baran, Daniela Čiháková
Myocarditis is the inflammation of the muscle tissues of the heart (myocardium). After a pathologic cardiac-specific inflammatory process, it may progress to chronic damage and dilated cardiomyopathy. The latter is characterized by systolic dysfunction, whose clinical correlate is heart failure. Nevertheless, other acute complications may arise as consequence of tissue damage and electrophysiologic disturbances. Different etiologies are involved in triggering myocarditis. In some cases, such as giant cell myocarditis or eosinophilic necrotizing myocarditis, it is an autoimmune process...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28528914/systemic-sclerosis-dermal-fibroblasts-suppress-th1-cytokine-production-via-galectin-9-overproduction-due-to-fli1-deficiency
#20
COMPARATIVE STUDY
Ryosuke Saigusa, Yoshihide Asano, Kouki Nakamura, Megumi Hirabayashi, Shunsuke Miura, Takashi Yamashita, Takashi Taniguchi, Yohei Ichimura, Takehiro Takahashi, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato
Dermal fibroblasts promote skin-localized transdifferentiation of regulatory T cells to T helper (Th) type 2-like cells in systemic sclerosis (SSc). However, the entire effect of SSc dermal fibroblasts on immune cells still remains unknown. Because galectin-9 induces Th2 cytokine-predominant immune imbalance by negatively regulating Th1/Th17 cells in inflammatory diseases, we investigated the contribution of galectin-9 to Th immune balance in SSc lesional skin. We used human clinical samples and Fli1(+/-) mice because Fli1 deficiency induces SSc-like phenotypes in various cell types...
September 2017: Journal of Investigative Dermatology
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