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https://www.readbyqxmd.com/read/29205464/interleukin-17-family-cytokines-in-protective-immunity-against-infections-role-of-hematopoietic-cell-derived-and-non-hematopoietic-cell-derived-interleukin-17s
#1
REVIEW
Goro Matsuzaki, Masayuki Umemura
Interleukin (IL)-17 family cytokines consisting of six members participate in immune response in infections, autoimmune diseases and inflammatory diseases. The prototype cytokine of the family, IL-17A, was originally identified from CD4+ T cells which are now termed Th17. Later IL-17A-producing cells are expanded to various hematopoietic cells including CD8+ T cells (Tc17), invariant NKT cells, γ δ T cells, non-T non-B lymphocytes termed type 3 innate lymphoid cells (ILC3), and neutrophils. Some members of the IL-17 family cytokines other than IL-17A were also expressed by CD4+ T cells: IL-17E by Th2 cells, and IL-17F by Th17 cells...
December 2, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/29187586/live-attenuated-leishmania-donovani-centrin-gene-deleted-parasites-induce-il-23-dependent-il-17-protective-immune-response-against-visceral-leishmaniasis-in-a-murine-model
#2
Antara Banerjee, Parna Bhattacharya, Pradeep K Dagur, Subir Karmakar, Nevien Ismail, Amritanshu B Joshi, Adovi D Akue, Mark KuKuruga, John Philip McCoy, Ranadhir Dey, Hira L Nakhasi
No vaccine exists against visceral leishmaniasis. To develop effective vaccines, we have previously reported protective role of live attenuated centrin gene-deleted Leishmania donovani (LdCen-/- ) parasites through induction of Th1 type immune response in mice, hamsters, and dogs. In this study, we specifically explored the role of Th17 cells in LdCen-/- -induced host protection in mice. Our results showed that compared with wild-type L. donovani infection, LdCen-/- parasites induce significantly higher expression of Th17 differentiation cytokines in splenic dendritic cells...
November 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29180433/a-stat3-dependent-transcriptional-circuitry-inhibits-cytotoxic-gene-expression-in-t-cells
#3
Thomas Ciucci, Melanie S Vacchio, Rémy Bosselut
CD8+ T cells are preprogrammed for cytotoxic differentiation in the thymus as they acquire expression of the transcription factor Runx3. However, a subset of effector CD8+ T cells (Tc17) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production, STAT3 and RORγt, inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok, which in CD4+ T cells restrains Runx3 functions and cytotoxicity; and STAT3 restrained cytotoxic gene expression in CD8+ T cells responding to viral infection in vivo...
November 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29175506/cd26-expression-is-down-regulated-on-cd8-t-cells-in-patients-with-hashimoto-s-thyroiditis
#4
Yalei Liu, Yuan Li, Yan Gong, Nan Yu, Yang Zhang, Ran You, Chenxue Qu, Guizhi Lu, Youyuan Huang, Ying Gao, Yanming Gao, Xiaohui Guo
The immune mechanism underlying Hashimoto's thyroiditis (HT) remains unclear. CD26, also known as dipeptidyl peptidase 4 (DPP-4), is a multifunctional molecule involved in the pathophysiology of autoimmune diseases. This study aimed to investigate the role of CD26 in the pathogenesis of HT. Peripheral blood was drawn from 20 healthy controls and 31 HT patients (19 mild HT patients and 12 severe HT patients). Plasma sCD26 concentrations were measured by ELISA, and sCD26 enzymatic activity was assessed using a luciferase-based assay...
November 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29108201/-clinical-features-of-imbalance-between-th1-and-th22-cells-and-its-association-with-disease-progression-in-patients-with-liver-cirrhosis
#5
H Q Wu, J J Zhao, H W Li, Z Zhang
Objective: To investigate the clinical features of imbalance between Th1 and Th22 cells and its association with disease progression in patients with liver cirrhosis, and to explore immune therapeutic strategies for targeted therapy for liver cirrhosis. Methods: In vitro peripheral blood mononucleated cells (PBMCs) were collected by centrifugation. CD3-BV500 and CD8-PerCP-Cy5.5 staining was performed for these cells. IFNγ-PE-Cy7, IL-17a-APC, IL-22-PE, or the corresponding isotype control was added, and then PBMCs were fixed with 1% polyoxymethylene after being washed once by permeabilization-wash buffer...
October 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29054368/an-intermediate-level-of-cd161-expression-defines-a-novel-activated-inflammatory-and-pathogenic-subset-of-cd8-t-cells-involved-in-multiple-sclerosis
#6
Bryan Nicol, Marion Salou, Isabel Vogel, Alexandra Garcia, Emilie Dugast, Jeremy Morille, Stéphanie Kilens, Eric Charpentier, Audrey Donnart, Steven Nedellec, Marylène Jacq-Foucher, Fabienne Le Frère, Sandrine Wiertlewski, Arnaud Bourreille, Sophie Brouard, Laure Michel, Laurent David, Pierre-Antoine Gourraud, Nicolas Degauque, Arnaud B Nicot, Laureline Berthelot, David-Axel Laplaud
Several lines of evidence support a key role for CD8(+) T cells in central nervous system tissue damage of patients with multiple sclerosis. However, the precise phenotype of the circulating CD8(+) T cells that may be recruited from the peripheral blood to invade the CNS remains largely undefined to date. It has been suggested that IL-17 secreting CD8 (Tc17) T cells may be involved, and in humans these cells are characterized by the expression of CD161. We focused our study on a unique and recently described subset of CD8 T cells characterized by an intermediate expression of CD161 as its role in neuroinflammation has not been investigated to date...
October 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29033080/reconstitution-of-th17-tc17-and-treg-cells-after-paediatric-haematopoietic-stem-cell-transplantation-impact-of-interleukin-7
#7
Katrine Kielsen, Lars P Ryder, David Lennox-Hvenekilde, Monika Gad, Claus H Nielsen, Carsten Heilmann, Marianne Ifversen, Anders Elm Pedersen, Klaus Müller
Successful reconstitution of T lymphocytes after allogeneic haematopoietic stem cell transplantation (HSCT) is needed to establish the graft-versus-leukaemia effect and an effective anti-microbial defense, but the ratio between functionally different T-cell subsets needs to be balanced to avoid graft-versus-host disease (GVHD). IL-7 is essential for T-cell generation in the thymus and peripheral T-cell homeostasis. High IL-7 levels have been associated with impaired T-cell reconstitution, increased risk of acute GVHD and treatment-related mortality, but the underlying cellular mechanisms behind these associations have not been investigated previously...
October 9, 2017: Immunobiology
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#8
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28900479/loss-of-tff1-promotes-pro-inflammatory-phenotype-with-increase-in-the-levels-of-ror%C3%AE-t-t-lymphocytes-and-il-17-in-mouse-gastric-neoplasia
#9
Mohammed Soutto, Mohamed Saleh, Mohamed S Arredouani, Blanca Piazuelo, Abbes Belkhiri, Wael El-Rifai
Background: TFF1 deficiency induces a mucosal pro-inflammatory phenotype that contributes to gastric tumorigenesis in mouse and human. Methods: We utilized the Tff1-KO mouse model to assess the impact of TFF1 loss on immune cells infiltration in the stomach. We used single cell suspension, flow cytometry, immunohistochemistry, and quantitative PCR (qPCR) assays. Results: The Tff1-KO gastric mucosa demonstrated high chronic inflammatory scores (score: 3-4) at age 2 months, which exacerbated at age 8 months (score: 4-6)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28874444/modulation-of-cd4-and-cd8-t-cell-function-and-cytokine-responses-in-strongyloides-stercoralis-infection-by-interleukin-27-il-27-and-il-37
#10
Rajamanickam Anuradha, Saravanan Munisankar, Yukthi Bhootra, Chandrakumar Dolla, Paul Kumaran, Thomas B Nutman, Subash Babu
Strongyloides stercoralis infection is associated with diminished antigen-specific Th1- and Th17-associated responses and enhanced Th2-associated responses. Interleukin-27 (IL-27) and IL-37 are two known anti-inflammatory cytokines that are highly expressed in S. stercoralis infection. We therefore wanted to examine the role of IL-27 and IL-37 in regulating CD4(+) and CD8(+) T cell responses in S. stercoralis infection. To this end, we examined the frequency of Th1/Tc1, Th2/Tc2, Th9/Tc9, Th17/Tc17, and Th22/Tc22 cells in 15 S...
November 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28757467/high-level-expression-and-purification-of-soluble-form-of-human-natural-killer-cell-receptor-nkr-p1-in-hek293s-gnti-cells
#11
Jan Bláha, Barbora Kalousková, Ondřej Skořepa, Samuel Pažický, Petr Novák, Ondřej Vaněk
Human natural killer receptor protein 1 (NKR-P1, CD161, gene klrb1) is a C-type lectin-like receptor of natural killer (NK) cells responsible for recognition of its cognate protein ligand lectin-like transcript 1 (LLT1). NKR-P1 is the single human orthologue of the prototypical rodent NKR-P1 receptors. Naturally, human NKR-P1 is expressed on the surface of NK cells, where it serves as inhibitory receptor; and on T and NKT cells functioning as co-stimulatory receptor promoting secretion of IFNγ. Most notably, it is expressed on Th17 and Tc17 lymphocytes where presumably promotes targeting into LLT1 expressing immunologically privileged niches...
December 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28741316/role-of-cd4-t-cell-helper-subsets-in-immune-response-and-deviation-of-cd8-t-cells-in-mice
#12
Alison Hogg, Yongjun Sui, Shlomo Z Ben-Sasson, William E Paul, Jay A Berzofsky
The ability of different CD4(+) T cell subsets to help CD8(+) T-cell response is not fully understood. Here, we found using the murine system that Th17 cells induced by IL-1β, unlike Th1, were not effective helpers for antiviral CD8 responses as measured by IFNγ-producing cells or protection against virus infection. However, they skewed CD8 responses to a Tc17 phenotype. Thus, the apparent lack of help was actually immune deviation. This skewing depended on both IL-21 and IL-23. To overcome this effect, we inhibited Th17 induction by blocking TGF-β...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28665747/analysis-of-immunological-mechanisms-exerted-by-hbsag-hbig-therapeutic-vaccine-combined-with-adefovir-in-chronic-hepatitis-b-patients
#13
Chenliang Zhou, Chaofan Li, Guo-Zhong Gong, Shuang Wang, Ji-Ming Zhang, Dao-Zhen Xu, Li-Min Guo, Hong Ren, Min Xu, Qing Xie, Chen Pan, Jie Xu, Zhongyu Hu, Shuang Geng, Xian Zhou, Xianzheng Wang, Xiaoyu Zhou, Haili Mi, Gan Zhao, Wencong Yu, Yu-Mei Wen, Lihua Huang, Xuan-Yi Wang, Bin Wang
An HBsAg-HBIG therapeutic vaccine (Yeast-derived Immune Complexes, YIC) for chronic hepatitis B (CHB) patients has undergone a series of clinical trials. The HBeAg sero-conversion rate of YIC varied from 21.9% to 14% depending on the immunization protocols from 6 to 12 injections. To analyze the immunological mechanisms exerted by 6 injections of YIC, 44 CHB patients were separately immunized with YIC, alum as adjuvant control or normal saline as blank control, with add on of antiviral drug Adefovir in all groups...
September 2, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28597107/microscopic-colitis-evolved-into-inflammatory-bowel-diseases-is-characterized-by-increased-th1-tc1-cells-in-colonic-mucosal-lamina-propria
#14
Ji Li, Yuchu Yan, Ziran Meng, Shuhong Liu, Paul L Beck, Subrata Ghosh, Jiaming Qian, Xianyong Gui
BACKGROUND: An association between microscopic colitis (MC), i.e., lymphocytic colitis (LC) and collagenous colitis (CC), and inflammatory bowel diseases (IBD) has been noticed. A subset of MC cases may evolve into IBD, and IBD in remission may present as MC in a histologic pattern. Moreover, MC and IBD may coexist in different regions of the bowel. A link between MC and IBD in their pathogenesis is, therefore, suggested. Abnormal mucosal immunity is likely the key. METHODS: We reviewed 2324 MC cases in Calgary over 14 years and identified 20 cases evolved into IBD (IBD transformers)...
October 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28558065/prediabetes-is-associated-with-the-modulation-of-antigen-specific-th1-tc1-and-th17-tc17-responses-in-latent-mycobacterium-tuberculosis-infection
#15
Nathella Pavan Kumar, Kadar Moideen, Chandrakumar Dolla, Paul Kumaran, Subash Babu
Type 2 diabetes mellitus (DM) is associated with the down modulation of Th1, Th2 and Th17 responses in latent Mycobacterium tuberculosis infection but the role of prediabetes (PDM) in this setting is not well understood. To examine the role of CD4+ and CD8+ T cell cytokines in latent tuberculosis (LTB) with coincident PDM, we studied the baseline, mycobacterial, control antigen and mitogen-stimulated T cell cytokine responses in LTB individuals with (LTB-PDM; n = 20) or without (LTB-NDM; n = 20) concomitant prediabetes...
2017: PloS One
https://www.readbyqxmd.com/read/28542595/antifungal-tc17-cells-are-durable-and-stable-persisting-as-long-lasting-vaccine-memory-without-plasticity-towards-ifn%C3%AE-cells
#16
Som Gowda Nanjappa, Andrew J McDermott, J Scott Fites, Kevin Galles, Marcel Wüthrich, George S Deepe, Bruce S Klein
Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells. We studied memory IL-17A+ CD8+ T-cell (Tc17) homeostasis, persistence and plasticity during fungal vaccine immunity. We report that vaccine-induced memory Tc17 cells persist with high fidelity to the type 17 phenotype. Tc17 cells persisted durably for a year as functional IL-17A+ memory cells without converting to IFNγ+ (Tc1) cells, although they produced multiple type I cytokines in the absence of residual vaccine antigen...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28474815/probiotic-supplementation-promotes-a-reduction-in-t-cell-activation-an-increase-in-th17-frequencies-and-a-recovery-of-intestinal-epithelium-integrity-and-mitochondrial-morphology-in-art-treated-hiv-1-positive-patients
#17
Gabriella d'Ettorre, Giacomo Rossi, Carolina Scagnolari, Mauro Andreotti, Noemi Giustini, Sara Serafino, Ivan Schietroma, Giuseppe Corano Scheri, Saeid Najafi Fard, Vito Trinchieri, Paola Mastromarino, Carla Selvaggi, Silvia Scarpona, Gianfranco Fanello, Fausto Fiocca, Giancarlo Ceccarelli, Guido Antonelli, Jason M Brenchley, Vincenzo Vullo
INTRODUCTION: HIV infection is characterized by a persistent immune activation associated to a compromised gut barrier immunity and alterations in the profile of the fecal flora linked with the progression of inflammatory symptoms. The effects of high concentration multistrain probiotic (Vivomixx®, Viale del Policlinico 155, Rome, Italy in EU; Visbiome®, Dupont, Madison, Wisconsin in USA) on several aspects of intestinal immunity in ART-experienced HIV-1 patients was evaluated. METHODS: A sub-study of a longitudinal pilot study was performed in HIV-1 patients who received the probiotic supplement twice a day for 6 months (T6)...
September 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28446465/deletion-of-lactate-dehydrogenase-a-in-myeloid-cells-triggers-antitumor-immunity
#18
Pankaj Seth, Eva Csizmadia, Andreas Hedblom, Marta Vuerich, Han Xie, Mailin Li, Maria Serena Longhi, Barbara Wegiel
Immunometabolism is emerging as a critical determinant of cancer pathophysiology. In this study, we explored the contributions of macrophage-expressed lactate dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of macrophages with a CD86(high) and MCP-1(high) M1-like phenotype that suppressed tumor growth. This phenotypic effect was accompanied by reduced VEGF expression and angiogenesis, diminished numbers of PD-L1(+) cancer cells, increased numbers of CD3(+) T cells, and activation status of CD8(+) T cells...
July 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28346024/increased-il-4-and-il-17-producing-cd8-cells-are-related-to-decreased-cd39-cd4-foxp3-cells-in-allergic-asthma
#19
Ping Li, Qun-Zhen Yang, Wei Wang, Gu-Qin Zhang, Jiong Yang
OBJECTIVE: In allergic asthma, regulatory T cell (Treg) number and function are decreased. Antigen-primed CD8(+) T cells play an indispensable role in the full development of airway inflammation and airway hyper-responsiveness (AHR) occurring in asthma. In this study, we investigated the relationship between subpopulations of CD8(+) T cells and CD39(+) Tregs. METHODS: Female C57BL/6 mice were used to develop the model of allergic asthma. Experimental mice were immunized with ovalbumin (OVA) by intra-peritoneal (i...
March 27, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28344884/the-differentiation-and-plasticity-of-tc17-cells-are-regulated-by-ctla-4-mediated-effects-on-stats
#20
Aditya Arra, Holger Lingel, Benno Kuropka, Jonas Pick, Tina Schnoeder, Thomas Fischer, Christian Freund, Mandy Pierau, Monika C Brunner-Weinzierl
As the blockade of inhibitory surface-molecules such as CTLA-4 on T cells has led to recent advances in antitumor immune therapy, there is great interest in identifying novel mechanisms of action of CD8(+) T cells to evoke effective cytotoxic antitumor responses. Using in vitro and in vivo models, we investigated the molecular pathways underlying the CTLA-4-mediated differentiation of IL-17-producing CD8(+) T cells (Tc17 cells) that strongly impairs cytotoxicity. Our studies demonstrate that Tc17 cells lacking CTLA-4 signaling have limited production of STAT3-target gene products such as IL-17, IL-21, IL-23R and RORγt...
2017: Oncoimmunology
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