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Paoul S Martinez, Eric S Storey, Cherie M Pucheu-Haston
OBJECTIVES: The purpose of this pilot study was to use a multiplexed assay to measure cytokines in normal stimulated canine tears. METHODS: 25 healthy dogs were included in the study. Stimulated tears were collected in capillary tubes from the right (OD) and left (OS) eyes and stored at -80 °C until batch sample analysis was performed. The samples were analyzed utilizing Luminex® canine-validated multiplex beads on a Bio-Rad multiplex analyzer for IL-2, IL-6, IL-7, IL-8, IL-10, TNF-α, and IFN-γ...
July 2018: Veterinary Immunology and Immunopathology
Vera Buchele, Benjamin Abendroth, Maike Büttner-Herold, Tina Vogler, Johanna Rothamer, Sakhila Ghimire, Evelyn Ullrich, Ernst Holler, Markus F Neurath, Kai Hildner
Intestinal graft-versus-host disease (GvHD) is a life-threatening, inflammatory donor T cell-mediated complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the light of the reported efficacy of interleukin-23 (IL-23)-blockade to mitigate syngeneic intestinal inflammation in inflammatory bowel disease patients, targeting IL-23 and thereby interleukin-17a (IL-17a) producing T helper (Th17) cells as the T cell subset assumed to be mostly regulated by IL-23, has emerged as a putatively general concept to harness immune-mediated mucosal inflammation irrespective of the underlying trigger...
2018: Frontiers in Immunology
Sabrina Giampaolo, Gabriela Wójcik, Stefan Klein-Hessling, Edgar Serfling, Amiya K Patra
B cell development in bone marrow is a precisely regulated complex process. Through successive stages of differentiation, which are regulated by a multitude of signaling pathways and an array of lineage-specific transcription factors, the common lymphoid progenitors ultimately give rise to mature B cells. Similar to early thymocyte development in the thymus, early B cell development in bone marrow is critically dependent on IL-7 signaling. During this IL-7-dependent stage of differentiation, several transcription factors, such as E2A, EBF1, and Pax5, among others, play indispensable roles in B lineage specification and maintenance...
June 15, 2018: Cellular & Molecular Immunology
Kristen M Reeder, Chad W Dunaway, Jonathan P Blackburn, Zhihong Yu, Sadis Matalon, Annette T Hastie, Elizabeth J Ampleford, Deborah A Meyers, Chad Steele
Asthmatics sensitized to fungi are reported to have more severe asthma, yet the immunopathogenic pathways contributing to this severity have not been identified. In a pilot assessment of human asthmatics, those subjects sensitized to fungi demonstrated elevated levels of the common γ-chain cytokine IL-7 in lung lavage fluid, which negatively correlated with the lung function measurement PC20. Subsequently, we show that IL-7 administration during experimental fungal asthma worsened lung function and increased the levels of type 2 cytokines (IL-4, IL-5, IL-13), proallergic chemokines (CCL17, CCL22) and proinflammatory cytokines (IL-1α, IL-1β)...
June 15, 2018: Mucosal Immunology
Reetta Vanhanen, Anni Tuulasvaara, Joonatan Mattila, Tommi Pätilä, T Petteri Arstila
Thymic commitment of human FOXP3+ regulatory T cells begins at the double positive (DP) CD4+ CD8+ stage. In the current study we show that interleukin-2 promotes the development of FOXP3+ thymocytes and enhances their survival at the DP phase. IL-2 increases the frequency of FOXP3+ cells and promotes the Treg phenotype after TCR-mediated positive selection at the most mature DP stage. However, it has no effect on FOXP3+ cells at the earlier maturation steps before positive selection. DP FOXP3+ are highly susceptible to cell death but IL-2 promotes their survival...
June 15, 2018: Scandinavian Journal of Immunology
Małgorzata Krzystek-Korpacka, Marek Zawadzki, Krzysztof Szufnarowski, Iwona Bednarz-Misa, Sabina Gorska, Wojciech Witkiewicz, Andrzej Gamian
Interleukin-7 is critical for T-cell development and displays antimicrobial and antitumor properties. It is referred to as a "critical enhancer of protective immunity". However, there is no information on interleukin-7 dynamics following colorectal surgery. Moreover, although robot-assisted surgery is gaining popularity, data on the immune response to it is almost non-existent. In this prospective non-randomized case-control study we found interleukin-7 dynamics to differ following robot-assisted and open approach and to affect postoperative immunity...
June 14, 2018: Scientific Reports
Qiuping Xu, Jie Shao, Shu Su, Jia Wei, Fangjun Chen, Fanyan Meng, Yang Zhao, Juan Du, Zhengyun Zou, Xiaoping Qian, Baorui Liu
Adoptive cell therapy (ACT) of autologous tumor-infiltrating lymphocytes (TILs) has shown an effect on mediating tumor regression in some patients with highly advanced, refractory metastatic malignancy. Here, the in vitro generation of TILs isolated from malignant pleural effusion and ascites was compared with which using engineered cells for costimulatory enhancement (ECCE) and 3 common γ-chain cytokines, interleukin (IL)-2, IL-7, and IL-15, alone or in combination. We showed the robust clinical-scale production of TILs with a less differentiated 'young' phenotype by expansion in the presence of ECCE combined with IL-2/7/15...
April 17, 2018: Cellular Immunology
Anna F Piotrowski, Thomas R Nirschl, Esteban Velarde, Lee Blosser, Sudipto Ganguly, Kathleen H Burns, Leo Luznik, John Wong, Charles G Drake, Stuart A Grossman
Severe radiation-related lymphopenia is common and associated with decreased survival in patients with several solid tumors. As the mechanisms underlying systemic lymphopenia are poorly understood, we developed an animal model to study the effects of brain radiation on lymphocytes and cytokines. C57 BL/6 and BALB/c mice received focal brain irradiation (4 Gy x 10 fractions or 2 Gy x 30 fractions). Weekly total lymphocyte counts (TLC), lymphocyte subsets and cytokines in blood and lymph nodes were measured...
2018: Oncoimmunology
Dewan Zhao, Lingjia Liu, Qiang Chen, Fangfang Wang, Qiuyang Li, Qiang Zeng, Jingcao Huang, Maowen Luo, Wenxian Li, Yuhuan Zheng, Ting Liu
BACKGROUND: The physiological approach suggests that an environment associating mesenchymal stromal cells with low O2 concentration would be most favorable for the maintenance of hematopoietic stem/progenitor cells (HSPCs). To test this hypothesis, we performed a coculture of cord blood CD34+ cells with Wharton's jelly mesenchymal stem cells (WJ-MSCs) under different O2 concentration to simulate the growth of HSPCs in vivo, and assessed the impacts on stemness maintenance and proliferation of cord blood HSPCs in vitro...
June 13, 2018: Stem Cell Research & Therapy
Kevin C Conlon, Milos D Miljkovic, Thomas A Waldmann
Cytokines are major regulators of innate and adaptive immunity that enable cells of the immune system to communicate over short distances. Cytokine therapy to activate the immune system of cancer patients has been an important treatment modality and continues to be a key contributor to current clinical cancer research. Interferon alpha (IFNα) is approved for adjuvant treatment of completely resected high-risk melanoma patients and several refractory malignancies. High-dose interleukin-2 (HDIL-2) is approved for treatment of metastatic renal cell cancer and melanoma, but both agents are currently less commonly used with the development of newer agents...
June 11, 2018: Journal of Interferon & Cytokine Research
Chie Watanabe, Geraldine L Shu, Natalia V Giltiay, Edward A Clark
The caspase (Casp) family of proteases regulate both lymphocyte apoptosis and activation. Here we show that Casp6 regulates early B cell development. One week-old Casp6 knockout (Casp6 KO) mice have significantly more splenic B cell subsets than wildtype (WT) mice. Adult Casp6 KO mice have normal levels of total splenic B cells but have increased numbers of B1a B cells and CD43+ 'transitional' or splenic red pulp (RP) B cells. These results suggested that Casp6 may function to control B cell numbers under non-homeostatic conditions and during B cell development...
June 4, 2018: Immunology and Cell Biology
Bei-Ying Zhang, Bing-Yun Wang, Shao-Chuan Li, Dong-Zhang Luo, Xiaoshu Zhan, Sheng-Feng Chen, Zhi-Sheng Chen, Can-Ying Liu, Hui-Qin Ji, Yin-Shan Bai, Dong-Sheng Li, Yang He
Objective: The aim of this study was to assess the efficacy of canine umbilical cord mesenchymal stem cells (UC-MSCs) on the treatment of knee osteoarthritis in dogs. Methods: Eight dogs were evenly assigned to two groups. The canine model of knee osteoarthritis was established by surgical manipulation of knee articular cartilage on these eight dogs. UC-MSCs were isolated from umbilical cord Wharton's jelly by 0.1% type collagenase I and identified by immunofluorescence staining and adipogenic and osteogenic differentiation in vitro ...
2018: Stem Cells International
Sara Martínez-López, Beatriz Sarriá, R Mateos, Laura Bravo-Clemente
PURPOSE: Coffee is rich in bioactive compounds with health beneficial properties, with green coffee presenting higher phenol content than roasted. We evaluated the effects of regularly consuming realistic amounts of a green/roasted coffee blend on cardiovascular health-related biomarkers. METHODS: A randomized, cross-over, controlled study was carried out in 25 normocholesterolemic [total cholesterol (TC) < 200 mg/dL] and 27 hypercholesterolemic (TC 200-240 mg/dL) subjects...
June 1, 2018: European Journal of Nutrition
James D Lord, S Alice Long, Donna M Shows, Jerill Thorpe, Katherine Schwedhelm, Janice Chen, Mariko Kita, Jane H Buckner
Integrin alpha4/beta7 on circulating lymphocytes identifies them as gut-tropic, and can be targeted by the humanized antibody vedolizumab to treat inflammatory bowel disease (IBD). We found lymphocytes expressing alpha4/beta7 were significantly more responsive to the pro-inflammatory cytokines IL-6, IL-7, and IL-21, and less responsive to the regulatory T cell (Treg)-supporting cytokine IL-2. Alpha4/beta7 was expressed by a smaller percent of FOXP3 + Helios+ thymically-derived Tregs (tTregs) than FOXP3 + Helios- peripherally-derived Tregs (pTregs) or FOXP3- effector T cells...
May 26, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Päivi Sirniö, Anne Tuomisto, Taina Tervahartiala, Timo Sorsa, Kai Klintrup, Toni Karhu, Karl-Heinz Herzig, Jyrki Mäkelä, Tuomo J Karttunen, Tuula Salo, Markus J Mäkinen, Juha P Väyrynen
BACKGROUND: Matrix metalloproteinase-8 (MMP-8) is a protease mainly expressed by neutrophils that cleaves numerous substrates, including collagens and cytokines. We have previously shown that serum MMP-8 levels increase in colorectal cancer (CRC) and correlate with distant metastasis. However, short follow-up in our prospective cohort did not enable survival analyses at the time of the first publication. METHODS: Preoperative serum MMP-8 levels were measured by immunofluorometric assay in 271 CRC patients and related to clinicopathological parameters, markers of systemic inflammation (modified Glasgow Prognostic Score, mGPS; serum levels of C-reactive protein (CRP), albumin and 13 cytokines), the density of six types of tumour-infiltrating immune cells and survival...
May 29, 2018: British Journal of Cancer
Malgorzata Krzystek-Korpacka, Marek Zawadzki, Bartosz Kapturkiewicz, Paulina Lewandowska, Iwona Bednarz-Misa, Sabina Gorska, Wojciech Witkiewicz, Andrzej Gamian
Colorectal cancers (CRCs) are treated as one entity but are in fact a heterogeneous group of diseases. If not addressed, subsite-associated variability may interfere with mechanism-targeted therapies and accuracy of potential CRC biomarkers. Little is known about the contribution of systemic inflammatory and immune mediators to subsite heterogeneity in CRC. Our purpose was to compare the profiles of key cytokines between right and left colonic and rectal CRCs. Using Luminex xMAP® technology, serum concentrations of eotaxin, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17, IFNγ, IP-10, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α and β, PDGF-BB, RANTES, TNFα, and VEGF-A were determined in 104 CRC patients...
May 22, 2018: Cytokine
Anuradha Rajamanickam, Saravanan Munisankar, Yukti Bhootra, Chandra Kumar Dolla, Kannan Thiruvengadam, Thomas B Nutman, Subash Babu
BACKGROUND: CD4+ and CD8+ T cells are central players in immunity to helminth infections. However, the role of T cell subsets in human helminth infections is not well understood. In addition, the common γc cytokines, IL-2, IL-4, IL-7, IL-9 and IL-15 play an important role in the maintenance of these CD4+ and CD8+ T cell subsets. METHODS: To examine the major T cell subsets and their association with the common γc cytokines, the absolute numbers of CD4+ and CD8+ naïve, central memory, effector memory and effector cells and the plasma levels of IL-2, IL-4, IL-7, IL-9 and IL-15 were measured in Strongyloides stercoralis (Ss) infected (INF, n = 60), helminth-uninfected (UN, n = 58) and in post treatment INF individuals...
May 24, 2018: PLoS Neglected Tropical Diseases
Taisuke Kondo, Yuuki Imura, Shunsuke Chikuma, Sana Hibino, Setsuko Omata-Mise, Makoto Ando, Takashi Akanuma, Mana Iizuka, Ryota Sakai, Rimpei Morita, Akihiko Yoshimura
Adoptive T cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen-specific stem cell memory T (TSCM ) cells is expected to overcome this shortcoming since TSCM cells are close to naïve T cells, but are also highly proliferative, long-lived, and produce a large number of effector T cells in response to antigen stimulation...
May 23, 2018: Cancer Science
Sergio Serrano-Villar, María de Lagarde, Jorge Vázquez-Castellanos, Alejandro Vallejo, J Ignacio Bernadino, Nadia Madrid, Mariano Matarranz, Alberto Díaz-Santiago, Carolina Gutiérrez, Alfonso Cabello, Judit Villar-García, José Ramón Blanco, Otilia Bisbal, Talía Sainz, Andrés Moya, Santiago Moreno, María José Gosalbes, Vicente Estrada
Background: While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, their clinical implications in HIV-infected subjects initiating ART at advanced HIV disease remain unclear. Methodology: Pilot multicenter randomized, placebo-controlled, double-blind study in which 78 HIV-infected, ART-naive subjects with <350 CD4 T-cells/µl or AIDS were randomized to either daily PMT25341 (a mixture of prebiotics, probiotics, oligonutrients, DHA, EPA, GLA, and aminoacids) or placebo for 48 weeks, each in combination with first-line ART...
May 16, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Jéssica Barletto de Sousa Barros, Paulo Alex Neves da Silva, Rosemary de Carvalho Rocha Koga, Patrícia Gonzalez-Dias, José Rodrigues Carmo Filho, Patrícia Resende Alo Nagib, Verônica Coelho, Helder I Nakaya, Simone Gonçalves Fonseca, Irmtraut Araci Hoffmann Pfrimer
An early immune response to Zika virus (ZIKV) infection may determine its clinical manifestation and outcome, including neurological effects. However, low-grade and transient viremia limits the prompt diagnosis of acute ZIKV infection. We have investigated the plasma cytokine, chemokine, and growth factor profiles of 36 individuals from an endemic area displaying different symptoms such as exanthema, headache, myalgia, arthralgia, fever, hyperemia, swelling, itching, and nausea during early-phase infection...
2018: Frontiers in Immunology
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