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https://www.readbyqxmd.com/read/29678672/genetic-restriction-of-antigen-presentation-dictates-allergic-sensitization-and-disease-in-humanized-mice
#1
Alina Neunkirchner, Bernhard Kratzer, Cordula Köhler, Ursula Smole, Lukas F Mager, Klaus G Schmetterer, Doris Trapin, Victoria Leb-Reichl, Edward Rosloniec, Ronald Naumann, Lukas Kenner, Beatrice Jahn-Schmid, Barbara Bohle, Rudolf Valenta, Winfried F Pickl
BACKGROUND: Immunoglobulin(Ig)E-associated allergies result from misguided immune responses against innocuous antigens. CD4+ T lymphocytes are critical for initiating and perpetuating that process, yet the crucial factors determining whether an individual becomes sensitized towards a given allergen remain largely unknown. OBJECTIVE: To determine the key factors for sensitization and allergy towards a given allergen. METHODS: We here created a novel human T cell receptor(TCR) and human leucocyte antigen (HLA)-DR1 (TCR-DR1) transgenic mouse model of asthma, based on the human-relevant major mugwort (Artemisia vulgaris) pollen allergen Art v 1 to examine the critical factors for sensitization and allergy upon natural allergen exposure via the airways in the absence of systemic priming and adjuvants...
April 5, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29673901/the-role-of-syk-in-peripheral-t-cells
#2
Jeoung-Eun Park, Sirshendu Majumdar, David D Brand, Edward F Rosloniec, Ae-Kyung Yi, John M Stuart, Andrew H Kang, Linda K Myers
The aim of this study was to understand how Syk affects peripheral T cell function. T cells from Syk-/- chimeric mice and DR1 Sykfl/fl CD4cre conditional mice gave strong CD3-induced Th1, Th2, and Th17 cytokine responses. However, an altered peptide ligand (APL) of human CII (256-276) with two substitutions (F263N, E266D), also called A12, elicited only Th2 cytokine responses from Sykfl/fl T cells but not Sykfl/fl- CD4cre T cells. Western blots revealed a marked increase in the phosphorylation of Syk, JNK and p38 upon A12/DR1 activation in WT or Sykfl/fl T cells but not in Sykfl/fl CD4-cre cells...
April 16, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29670037/expression-and-regulation-of-thymic-stromal-lymphopoietin-and-thymic-stromal-lymphopoietin-receptor-heterocomplex-in-the-innate-adaptive-immunity-of-pediatric-asthma
#3
REVIEW
Sheng-Chieh Lin, Fang-Yi Cheng, Jun-Jen Liu, Yi-Ling Ye
Asthma is a chronic inflammatory disease affecting the airway, and it is characterized by a wheezing breathing sound, variable airflow obstruction and the presence of inflammatory cells in the submucosa of the bronchi. Viral infection, pollutants and sensitivity to aeroallergens damage the epithelium from childhood, which causes asthma. The pathogenesis of asthma includes pathways of innate stimulation by environmental microbes and irritant pathogens. Damaged epithelial cells produce thymic stromal lymphopoietin (TSLP) and stimulate myeloid dendritic cell maturation through the thymic stromal lymphopoietin receptor (TSLPR) heterocomplex...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29669333/the-role-of-proteasome-inhibitor-mg132-in-2-4-dinitrofluorobenzene-induced-atopic-dermatitis-in-nc-nga-mice
#4
Kozo Ohkusu-Tsukada, Daiki Ito, Kimimasa Takahashi
BACKGROUND: Although immunosuppressants for therapy of atopic dermatitis (AD) are still being sought, proteasome inhibitors are also potential candidates for the treatment of AD. Proteasome inhibitors exert various effects by blocking proteasomal degradation and help regulate processes such as apoptosis induction via caspase-9, cell cycle progression via cyclins, NF-κB inactivation via IκB, and downregulation of antigen cross-presentation. The cells targeted by proteasome inhibitors are therefore activated cells undergoing proliferation or differentiation, and antigen-presenting cells carrying out protein degradation...
April 18, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29662488/subretinal-injection-of-hy-peptides-induces-systemic-antigen-specific-inhibition-of-effector-cd4-and-cd8-t-cell-responses
#5
Julie Vendomèle, Safa Dehmani, Quentin Khebizi, Anne Galy, Sylvain Fisson
Purpose: Injection of an antigen into the anterior chamber of the eye induces a peripheral antigen-specific immune modulation mechanism, known as anterior chamber-associated immune deviation (ACAID). Delayed-type hypersensitivity experiments argue that the subretinal space (SR) of the eye displays properties similar to ACAID. However, no investigation was performed regarding the differential impact of a subretinal antigen injection on peripheral CD4+ versus CD8+ T cells, on the potential immune deviation regarding Th profiles, and on the antigen-specificity of the inhibition...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29660515/aspergillus-fumigatus-viability-drives-allergic-responses-to-inhaled-conidia
#6
Ajay P Nayak, Tara L Croston, Angela R Lemons, W T Goldsmith, Nikki B Marshall, Michael L Kashon, Dori R Germolec, Donald H Beezhold, Brett J Green
BACKGROUND: Aspergillus fumigatus induced allergic airway disease has been shown to involve conidial germination in vivo but the immunological mechanisms remain uncharacterized. OBJECTIVE: A subchronic murine exposure model was used to examine the immunological mediators that are regulated in response to either culturable or non-culturable A. fumigatus conidia. METHODS: Female B6C3F1/N mice were repeatedly dosed via inhalation with 1 x 105 viable or heat inactivated conidia (HIC), twice a week for 13 weeks (26 exposures)...
April 13, 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29660300/the-major-orphan-forms-of-ichthyosis-are-characterized-by-systemic-t-cell-activation-and-th-17-tc-17-th-22-tc22-polarization-in-blood
#7
Tali Czarnowicki, Helen He, Alexandra Leonard, Kunal Malik, Shai Magidi, Stephanie Rangel, Krishna Patel, Kara Ramsey, Morgan Murphrey, Teresa Song, Yeriel Estrada, Hue-Chi Wen, James G Krueger, Emma Guttman-Yassky, Amy S Paller
The ichthyoses are rare skin disorders with immune and barrier aberrations. Identifying blood phenotypes may advance targeted-therapeutics.We aimed to compare frequencies of skin homing/CLA+ vs. systemic/CLA- "polar" CD4+ /CD8+ and activated T-cell subsets in ichthyosis vs. atopic dermatitis/AD, psoriasis and control blood, with appropriate clinical correlations. Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+ /CD8+ T-cells, with ICOS and HLA-DR defining mid- and long-term T-cell activation, respectively...
April 13, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29649855/a-salmonella-typhi-ghost-induced-by-the-e-gene-of-phage-%C3%AF-x174-stimulates-dendritic-cells-and-efficiently-activates-the-adaptive-immune-response
#8
Gayeon Won, Seong Kug Eo, Sang-Youel Park, Jin Hur, John Hwa Lee
We previously genetically engineered a Salmonella Typhi bacterial ghost (STG) as a novel inactivated vaccine candidate against typhoid fever. The underlying mechanism employed by the ghost to stimulate the adaptive immune response remains to be investigated. In this study, we aimed to evaluate the immunostimulatory effect of STG on mouse bone marrow-derived dendritic cells (BMDCs) and its activation of the adaptive immune response in vitro . Immature BMDCs were stimulated with STG, which efficiently stimulated maturation events in BMDCs, as indicated by up-regulated expression of CD40, CD80, and MHC-II molecules on CD11+ BMDCs...
April 12, 2018: Journal of Veterinary Science
https://www.readbyqxmd.com/read/29649688/recombinant-outer-membrane-protein-25c-from-brucella-abortus-induces-th1-and-th2-mediated-protection-against-brucella-abortus-infection-in-mouse-model
#9
Soumya Paul, Bhavani V Peddayelachagiri, Sowmya Nagaraj, Joseph J Kingston, Harsh V Batra
Development of a safe and efficacious vaccine for brucellosis is a long standing challenge for scientists. Recognizing potential antigens towards developing vaccine candidate is crucial. Omp25c, a porin protein of Brucella, is a paralog of two previously identified promising vaccine candidates namely, Omp25 and Omp31, with notable sequence identity. Also, Omp25c is conserved in all major Brucella species. This highlights the possibility of employing this protein in multivalent subunit vaccine based approach of Brucella management...
April 9, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29627388/gaba-regulates-release-of-inflammatory-cytokines-from-peripheral-blood-mononuclear-cells-and-cd4-t-cells-and-is-immunosuppressive-in-type-1-diabetes
#10
Amol K Bhandage, Zhe Jin, Sergiy V Korol, Qiujin Shen, Yu Pei, Qiaolin Deng, Daniel Espes, Per-Ola Carlsson, Masood Kamali-Moghaddam, Bryndis Birnir
The neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule in the brain and in pancreatic islets. Here, we demonstrate that GABA regulates cytokine secretion from human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells. In anti-CD3 stimulated PBMCs, GABA (100nM) inhibited release of 47 cytokines in cells from patients with type 1 diabetes (T1D), but only 16 cytokines in cells from nondiabetic (ND) individuals. CD4+ T cells from ND individuals were grouped into responder or non-responder T cells according to effects of GABA (100nM, 500nM) on the cell proliferation...
March 28, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29626493/profiling-calcium-signals-of-in-vitro-polarized-human-effector-cd4-t-cells
#11
Sarah Kircher, Maylin Merino-Wong, Barbara A Niemeyer, Dalia Alansary
Differentiation of naïve CD4+ T cells into effector subtypes with distinct cytokine profiles and physiological roles is a tightly regulated process, the imbalance of which can lead to an inadequate immune response or autoimmune disease. The crucial role of Ca2+ signals, mainly mediated by the store operated Ca2+ entry (SOCE) in shaping the immune response is well described. However, it is unclear if human effector CD4+ T cell subsets show differential Ca2+ signatures in response to different stimulation methods...
April 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29620252/tim%C3%A2-4-blockade-of-kcs-combined-with-exogenous-tgf%C3%A2-%C3%AE-injection-helps-to-reverse-acute-rejection-and-prolong-the-survival-rate-of-mice-receiving-liver-allografts
#12
Hao Wu, Xuesong Xu, Jinzheng Li, Jianping Gong, Min Li
An acute reaction response (AR) following liver transplantation (LT) is caused by immune responses that are primarily mediated by T lymphocytes. Kupffer cells (KCs) are the largest antigen presenting cell (APC) group in vivo and are the primary modulators of the inflammatory or tolerogenic immune response in liver tissues. T cell immunoglobulin‑domain and mucin‑domain-4 (TIM‑4), the only TIM protein not expressed on T cells, is expressed on APCs; suggesting that it mediates the various immune responses...
March 30, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29610847/the-imbalance-of-lymphocyte-subsets-and-cytokines-potential-immunologic-insights-into-the-pathogenesis-of-chronic-dacryocystitis
#13
Xiaoxuan Yang, Lizhen Wang, Lunhao Li, Zhang Yu, Caiwen Xiao
Purpose: To explore the quantitative distributions of different lymphocyte subsets in the lacrimal sac mucosa and identify changes of Th1- and Th2-associated cytokines in the tears of patients with chronic dacryocystitis. Methods: Lacrimal sac mucosal specimens from patients with chronic dacryocystitis were analyzed. Hematoxylin-eosin staining and Masson staining were performed for pathologic analysis, and immunohistochemical staining was performed for the detection of CD3+, CD4+, CD8+, CD20+, Th1, and Th2 lymphocytes...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29599090/intranasal-but-not-subcutaneous-vaccination-with-laag-allows-rapid-expansion-of-protective-immunity-against-cutaneous-leishmaniasis
#14
Izabella Pereira Silva Bezerra, Marina Amaral Abib, Bartira Rossi-Bergmann
Mucosal but not parenteral vaccination with whole Leishmania amazonensis promastigotes antigens (LaAg) is known to increase host resistance to infection by an as yet unknown immune mechanism. Since early immune responses are critical for infection establishment, in the present study the differential responses elicited by subcutaneous (s.c.) and intranasal (i.n.) vaccination with LaAg were investigated during the initial stages of infection. For that, BALB/c mice were given two LaAg doses by i.n. or s.c. route prior to L...
March 26, 2018: Vaccine
https://www.readbyqxmd.com/read/29598931/tarc-expression-in-the-circulation-and-cutaneous-granulomas-correlates-with-disease-severity-and-indicates-th2-mediated-progression-in-patients-with-sarcoidosis
#15
Chuyen Thi Hong Nguyen, Naotomo Kambe, Ikuko Ueda-Hayakawa, Izumi Kishimoto, Nhung Thi My Ly, Kana Mizuno, Hiroyuki Okamoto
BACKGROUND: Sarcoidosis is a systemic disorder characterized by the accumulation of lymphocytes and monocyte/macrophage lineage cells that results in the formation of non-caseating granulomas. Thymus- and activation-regulated chemokine (TARC)/CCL17 is an important chemokine in the amplification of Th2 responses, which are achieved by recruiting CCR4-expressing CD4+ T lymphocytes. TARC concentrations are known to increase in the serum of sarcoidosis patients; however, its role in the assessment of severity and prognosis of sarcoidosis remains unknown...
March 26, 2018: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/29588155/identification-of-immunodominant-th2-cell-epitopes-in-chinese-bullous-pemphigoid-patients
#16
Jieyu Zhang, Hui Fang, Shengxian Shen, Erle Dang, Qiuju Li, Pei Qiao, Hongjiang Qiao, Gang Wang
Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease caused by autoantibodies (autoAbs) targeting the juxtamembranous extracellular noncollagenous 16A (NC16A) domain of human collagen XVII (also known as BP180). Because T helper cells are essential for antibody responses to antigens, we adopted an assay to map the immunodominant Th2-cell epitopes in NC16A. We synthesized 22 overlapping peptides spanning the entire sequence of BP180-NC16A and investigated the reactivity of Th2 cells from BP patients to these peptides using the ELISPOT assay...
March 24, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29581081/silencing-socs1-in-dendritic-cells-promote-survival-of-mice-with-systemic-candida-albicans-infection-via-inducing-th1-cell-differentiation
#17
Dongmei Shi, Dongmei Li, Qiong Wang, Xue Kong, Huan Mei, Yongnian Shen, Weida Liu
Enhancing the immunity conferred by dendritic cells (DCs) to fungal infection represents a promising strategy in the number of immunocompromised individuals. In a previous study, we demonstrated that suppressor of cytokine signaling 1 (SOCS1) silencing can promote the maturation of DCs and induce an immune response against Candida albicans (C. albicans) in vitro. Herein, the effectiveness of SOCS1 suppression administered by SOCS1-siRNA-treated DCs is further evaluated in systemic candidiasis mouse model. The SOCS1-silenced DCs increase mouse survival and significantly decrease fungal colonization in the kidneys...
March 23, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29577371/role-of-t-bet-the-master-regulator-of-th1-cells-in-the-cytotoxicity-of-murine-cd4-t-cells
#18
Koji Eshima, Kana Misawa, Chihiro Ohashi, Kazuya Iwabuchi
Although CD4+ T cells are generally regarded as helper T cells, some activated CD4+ T cells exert cytotoxicity. Since CD4+ cytotoxic T lymphocytes (CTLs) often secrete IFN-γ, CTL activity among CD4+ T cells may be attributable to Th1 cells, where a T-box family molecule, T-bet serves as the "master regulator". However, although the essential contribution of T-bet to the expression of IFN-γ has been well-documented, it remains unclear if T-bet is involved in CD4+ T cell-mediated cytotoxicity. In this study, in order to investigate the ability of T-bet to confer cytolytic activity on CD4+ T cells, we introduced the T-bet gene into non-cytocidal CD4+ T cell lines and analyzed their cytolytic function...
March 25, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29576879/the-balance-of-th1-th2-and-lap-tregs-th17-cells-is-crucial-for-graft-survival-in-allogeneic-corneal-transplantation
#19
Shang Li, Jing Yu, Chungang Guo, Ying Jie, Zhiqiang Pan
Purpose: CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs). The aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in mice after allogeneic corneal transplantation. Methods: A total of 65 mice received orthotopic penetrating transplantation. According to the survival scores of the grafts, the mice were divided into the rejection group and the survival group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in the ipsilateral drainage lymph nodes and spleens were measured with flow cytometry...
2018: Journal of Ophthalmology
https://www.readbyqxmd.com/read/29575251/treatment-for-moderate-to-severe-atopic-dermatitis-at-alpine-and-moderate-maritime-climates-differentially-affect-helper-t-cells-and-memory-b-cells-in-children
#20
Jorn J Heeringa, Karin B Fieten, Finola M Bruins, Els van Hoffen, Edward F Knol, Suzanne G M A Pasmans, Menno C van Zelm
BACKGROUND: Treatment of atopic dermatitis (AD) is focused on topical anti-inflammatory therapy, epidermal barrier repair and trigger avoidance. Multidisciplinary treatment in both moderate maritime and alpine climates can successfully reduce disease activity in children with AD. However, it remains unclear whether abnormalities in B- and T-cell memory normalize and if this differs between treatment strategies. OBJECTIVE: To determine whether successful treatment in maritime and alpine climates normalises B- and T-lymphocytes in children with moderate to severe AD...
March 25, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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