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Cd4 th2

Rakesh K Singh, Sreenivas Gannavaram, Nevien Ismail, Amit Kaul, Mallikarjuna Rao Gedda, Hira L Nakhasi
The protozoan parasite Leishmania has evolved several strategies to undermine host defense mechanisms by inducing Th2-type adaptive immunity and suppressing effector functions of Th1 phenotype. In our earlier studies, using centrin gene-deleted Leishmania (LdCen-/- ) parasites as an immunogen, we have shown induction of an effective Th1-type immunity and robust memory responses that mediate protection against virulent challenge. However, role of inhibitory signals in Leishmania vaccine induced immunity in general, and LdCen-/- in particular has not been studied...
2018: Frontiers in Immunology
Cong Wang, Weisheng Cheng, Qian Yu, Tian Xing, Shoubin Chen, Lei Liu, Li Yu, Jian Du, Qingli Luo, Jilong Shen, Yuanhong Xu
Toxoplasma gondii infection evokes a strong Th1-type response with interleukin (IL)-12 and interferon (IFN)-γ secretion. Recent studies suggest that the infection of pregnant mice with T. gondii may lead to adverse pregnancy results caused by subversion of physiological immune tolerance at maternofetal interface rather than direct invasion of the parasite. Genotype-associated dense granule protein GRA15II tends to induce classically activated macrophage (M1) differentiation and subsequently activating NK, Th1, and Th17 cells whereas rhoptry protein ROP16I/III drives macrophages to alternatively activated macrophage (M2) polarization and elicits Th2 immune response...
2018: Frontiers in Immunology
Melanie Sarah Prout, Ryan L Kyle, Franca Ronchese, Graham Le Gros
Although IL-4 is long associated with CD4 Th2 immune responses, its role in Th2 subset development in non-lymphoid tissues is less clear. We sought to better define IL-4's role in CD4 Th2 responses by using transgenic mice that express a dual IL-4 AmCyan/IL-13 DsRed (IL-4AC/IL-13DR) fluorescent reporter on an IL-4-sufficient or IL-4-deficient background. Using primary Th2 immune response models against house dust mite or Nippostrongylus brasiliensis ( Nb ) allergens, we examined the requirement for IL-4 by each of the defined Th2 subsets in the antigen draining lymph node, skin, and lung tissues...
2018: Frontiers in Immunology
Tomoe Nishimura, Osamu Kaminuma, Mayumi Saeki, Noriko Kitamura, Minoru Gotoh, Akio Mori, Takachika Hiroi
BACKGROUND: We have recently demonstrated that T cell-mediated nasal hyperresponsiveness (NHR) is a representative pathophysiological feature of allergic rhinitis (AR). Although several anti-allergic drugs are used for the treatment of AR, the efficacy of these drugs on T cell-mediated NHR have not been elucidated. In these studies we investigated the effects of dexamethasone (Dex), montelukast (Mk), and chlorpheniramine (Chl) on NHR in antigen-immunized and antigen-specific Th2 cell-transferred mice...
June 15, 2018: Allergology International: Official Journal of the Japanese Society of Allergology
Masaya Matsuda, Yuki Morie, Hirotaka Oze, Kana Doi, Tatsuya Tsutsumi, Junpei Hamaguchi, Miki Inaba, Takeshi Nabe
INTRODUCTION: The mechanisms of allergen immunotherapy are not fully elucidated. Here, we sought to develop a murine model to demonstrate the effectiveness of subcutaneous immunotherapy (SCIT) for allergic responses. As excessive antigen dosages may induce immune tolerance in sensitized mice, the effects of SCIT were assessed by varying the antigen dosage. The mechanisms of SCIT were analyzed by focusing on the induction of Foxp3+ Treg cells and IL-10-producing Foxp3- CD4+ T cells, as well as on the phenotype of the latter cells...
June 14, 2018: International Immunopharmacology
Daniel M Moldaver, Mantej S Bharhani, Christopher D Rudulier, Jennifer Wattie, Mark D Inman, Mark Larché
BACKGROUND: Treatment of cat allergic subjects with peptides derived from Fel d 1 (the major cat allergen) ameliorated symptoms of cat allergy in phase 2 clinical trials. OBJECTIVE: To demonstrate that the tolerance induced by Fel d 1 peptide immunotherapy can be exploited to reduce allergic responses to a second allergen, ovalbumin (OVA), in mice dually sensitized to OVA and Fel d 1. METHODS: The induction of tolerance to OVA was achieved via a simultaneous exposure to both allergens following peptide treatment...
June 12, 2018: Journal of Allergy and Clinical Immunology
Kazunori Yamada, Masahiko Zuka, Kiyoaki Ito, Keishi Mizuguchi, Yasushi Kakuchi, Tamehito Onoe, Yasunori Suzuki, Masakazu Yamagishi, Shozo Izui, Marie Malissen, Bernard Malissen, Mitsuhiro Kawano
BACKGROUND: The adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (LatY136F) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity...
2018: PloS One
Xiao Zhao, Juan Long, Fei Liang, Nan Liu, Yuying Sun, Yongzhi Xi
Antigen-specific tolerizing DNA vaccines are one of the most promising strategies for rheumatoid arthritis (RA) treatment, and act by inducing potent immune tolerance instead of generalized immunosuppression. Recently, we developed a novel antigen-specific tolerizing DNA vaccine coding for chicken type II collagen (pcDNA-CCOL2A1), and confirmed its potent therapeutic efficacy in an established rat model of collagen-induced arthritis (CIA). Here we report the prophylactic vaccination efficacy of a single 300ug/kg dose of pcDNA-CCOL2A1 against CIA incidence, severity, and onset...
June 14, 2018: Human Gene Therapy
Hyun-Young Jang, Jeung-Hyun Koo, Sang-Myeong Lee, Byung-Hyun Park
Previous clinical trials have addressed the beneficial effects of fish oil supplementation on atopic dermatitis. Recently, we reported that fat-1 mice, which can convert n-6 to n-3 polyunsaturated fatty acids (PUFAs), are protected against allergic airway inflammation because their Th2 immune responses are suppressed. Here, we examined the effects of endogenously synthesized n-3 PUFAs on atopic dermatitis, a representative Th2-dominant allergic inflammatory disease. Mouse models of atopic dermatitis-like skin lesions were prepared by epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) or house dust mite (HDM) extract to the ears...
June 13, 2018: Experimental & Molecular Medicine
Vanesa Cunill, Margarita Massot, Antonio Clemente, Carmen Calles, Valero Andreu, Vanessa Núñez, Antonio López-Gómez, Rosa María Díaz, María de Los Reyes Jiménez, Jaime Pons, Cristòfol Vives-Bauzà, Joana Maria Ferrer
Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease, although several evidences also demonstrate a B cell involvement in its etiology. Follicular T helper (Tfh) cells, a CXCR5-expressing CD4+ T cell subpopulation, are essential in the regulation of B cell differentiation and maintenance of humoral immunity. Alterations in circulating (c)Tfh distribution and/or function have been associated with autoimmune diseases including MS. Dimethyl fumarate (DMF) is a recently approved first-line treatment for relapsing-remitting MS (RRMS) patients whose mechanism of action is not completely understood...
2018: Frontiers in Immunology
Gopalsamy Rajiv Gandhi, Maria Terezinha Santos Leite Neta, Rajiv Gandhi Sathiyabama, Jullyana de Souza Siqueira Quintans, Ana Mara de Oliveira E Silva, Adriano Antunes de Souza Araújo, Narendra Narain, Lucindo José Quintans Júnior, Ricardo Queiroz Gurgel
BACKGROUND: Flavonoids are naturally occurring compounds, extensively distributed in plants. T helper (Th)1 and Th2 cytokines balance plays an essential role in the reaction of inflammatory, allergic and infectious processes and transplantation rejection. PURPOSE: This systematic review focuses on various classes of flavonoids with a view to evaluate whether Th1/Th2 cytokine-mediated pathways of immunoenhancement could reduce immune overwhelming reactions. METHODS: Articles in English published from inception to December 2017 reporting flavonoids with immunomodulatory activity for the management of immune-mediated disorders were acquired from PubMed, EMBASE, Scopus and Web of Science and a animal experiments where Th1 and Th2 cytokines were investigated to assess the outcome of immunoregulatory therapy were included...
May 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Handong Zheng, Dandan Wu, Xiang Wu, Xing Zhang, Qin Zhou, Yan Luo, Xin Yang, Cameron J Chock, Meilian Liu, Xuexian O Yang
Allergic asthma and obesity are major public health problems in the world. Recent Meta-analysis studies implicated a positive relationship between serum leptin, which is elevated in obese individuals, and the risk of asthma. However, it is not well understood how obesity-associated elevation of leptin increases the risk of asthma. In the current study, we have found that leptin induces the unfolded protein response factor XBP1s in an mTOR- and MAPK-dependent manner in pro-allergic TH2 cells; in vivo, mice fed with high fat diet had increased serum leptin as observed in human obese population and exacerbated asthmatic symptoms, associated with increased XBP1s expression in splenic CD4+ T cells...
June 11, 2018: Scientific Reports
Rosario Guadalupe Labastida-Conde, Oscar Ramírez-Pliego, Mercedes Peleteiro-Olmedo, Delia Vanessa Lopez-Guerrero, Oscar Daniel Badillo-Godinez, María de Lourdes Gutiérrez-Xicoténcatl, Gabriela Rosas-Salgado, África González-Fernández, Fernando R Esquivel-Guadarrama, M Angélica Santana
Neonates have an increased susceptibility to infections, particularly those caused by intracellular pathogens, leading to high morbidity and mortality rates. This is partly because of a poor response of neonatal CD4+ T cells, leading to deficient antibody production and a low production of IFN-γ, resulting in deficient elimination of intracellular pathogens. The poor memory response of human neonates has underpinned the need for improving vaccine formulations. Molecular adjuvants that improve the response of neonatal lymphocytes, such as the ligands of toll-like receptors (TLRs), are attractive candidates...
June 8, 2018: Vaccine
Zhenlong Luo, Yudong Ji, Dean Tian, Yong Zhang, Sheng Chang, Chao Yang, Hongmin Zhou, Zhonghua Klaus Chen
Galectin-7 (Gal-7) has been associated with cell proliferation and apoptosis. It is known that Gal-7 antagonises TGFβ-mediated effects in hepatocytes by interacting with Smad3. Previously, we have demonstrated that Gal-7 is related to CD4+ T cells responses; nevertheless, its effect and functional mechanism on CD4+ T cells responses remain unclear. The murine CD4+ T cells were respectively cultured with Gal-7, anti-CD3/CD28 mAbs, or with anti-CD3/CD28 mAbs & Gal-7. The effects of Gal-7 on proliferation and the phenotypic changes in CD4+ T cells were assessed by flow cytometry...
June 8, 2018: Molecular Immunology
Chuanlei Yang, Xing Chen, Zhanjie Wei, Jie Xiao, Weiqiang Chen, Yuqiang Shang, Jinping Liu
Acute rejection is the most important factor causing allograft loss, which remains a challenge for patients undergoing organ transplantation. There is considerable evidence indicating that the activity of PI3K and its downstream positive and negative regulators plays a major role in regulating the activation of different subsets of effector CD4+ T cells. Thus, we investigated whether class A PI3Ks are involved in the development of acute allograft rejection, we found that p110α protein expression levels in the allograft group were significantly up-regulated on day 7 post-transplantation, while p110β and p110δ expression was significantly increased on days 5 and 7 post-transplantation...
2018: American Journal of Translational Research
Mao-Gang Li, Xiao-Yu Liu, Zhi-Qiang Liu, Jing-Yi Hong, Jiang-Qi Liu, Cai-Jie Zhou, Tian-Yong Hu, Xiao-Jun Xiao, Pi-Xin Ran, Peng-Yuan Zheng, Zhi-Gang Liu, Ping-Chang Yang
The Th2-biased inflammation and immune deregulation play a critical role in the pathogenesis of ulcerative colitis (UC). Recent studies indicate that the Bcl2-like protein 12 (Bcl2L12) is associated with immune deregulation of UC. This study aims to investigate the role of Bcl2L12 in the induction of aberrant Th2-biased inflammation. In this study, peripheral blood samples were collected from patients with inflammatory bowel disease. The Th2 cell activities were analyzed by flow cytometry, real-time quantitative RT-PCR, and Western blotting...
June 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Jonatan Leffler, Philip A Stumbles, Deborah H Strickland
IgE sensitisation has increased significantly over the last decades and is a crucial factor in the development of allergic diseases. IgE antibodies are produced by B cells through the process of antigen presentation by dendritic cells, subsequent differentiation of CD4⁺ Th2 cells, and class switching in B cells. However, many of the factors regulating these processes remain unclear. These processes affect males and females differently, resulting in a significantly higher prevalence of IgE sensitisation in males compared to females from an early age...
May 23, 2018: International Journal of Molecular Sciences
Ayşe Kılıç, Marc Santolini, Taiji Nakano, Matthias Schiller, Mizue Teranishi, Pascal Gellert, Yuliya Ponomareva, Thomas Braun, Shizuka Uchida, Scott T Weiss, Amitabh Sharma, Harald Renz
Allergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including microRNAs (miRs), are pivotal in maintaining immune homeostasis. Since an altered expression of various miRs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRs control mechanisms ensuring Th2 stability and maintenance in the lung...
June 7, 2018: JCI Insight
Jeffrey M H Liu, Xiaomin Zhang, Shelby Joe, Xunrong Luo, Lonnie D Shea
Introduction: The development of novel immunomodulatory strategies that might decrease the need for systemic immune suppression would greatly enable the utility of cell-based therapies. Cell transplantation on biomaterial scaffolds offers a unique opportunity to engineer a site to locally polarize immunogenic antigen generation. Herein, we investigated the localized delivery of IL-33, which is a novel cytokine that has been shown to have beneficial immunomodulatory effects in certain transplant models as mediating anti-inflammatory properties in the adipose tissue, to determine its feasibility for use as an immunomodulatory agent...
March 2018: Journal of immunology and regenerative medicine
Anke Fähnrich, Sebastian Klein, Arnauld Sergé, Christin Nyhoegen, Sabrina Kombrink, Steffen Möller, Karsten Keller, Jürgen Westermann, Kathrin Kalies
CD154 is a transmembrane cytokine expressed transiently on activated CD4 T cells upon T-cell receptor (TCR) stimulation that interacts with CD40 on antigen-presenting cells. The signaling via CD154:CD40 is essential for B-cell maturation and germinal center formation and also for the final differentiation of CD4 T cells during T-dependent humoral immune responses. Recent data demonstrate that CD154 is critically involved in the selection of T-cell clones during the negative selection process in the thymus. Whether CD154 signaling influences the TCR repertoire during peripheral T-dependent humoral immune responses has not yet been elucidated...
2018: Frontiers in Immunology
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