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https://www.readbyqxmd.com/read/29155098/orai1-mutations-abolishing-store-operated-ca-2-entry-cause-anhidrotic-ectodermal-dysplasia-with-immunodeficiency-eda-id
#1
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 Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels is an essential signaling pathway in many cell types. CRAC channels are formed by ORAI1, ORAI2 and ORAI3 proteins and activated by stromal interaction molecule 1 (STIM1) and STIM2. Mutations in ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and non-immunological symptoms. OBJECTIVE: Molecular and immunological analysis of patients with CID, anhidrosis and ectodermal dysplasia of unknown etiology...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29135830/tissue-resident-lymphocytes-in-solid-organ-transplantation-innocent-passengers-or-the-key-to-organ-transplant-survival
#2
Amy C Prosser, Axel Kallies, Michaela Lucas
Short-term outcomes of solid organ transplantation have improved dramatically over the past several decades; however, long-term survival has remained static over the same time period, and chronic rejection remains a major cause of graft failure. The importance of donor, or 'passenger', lymphocytes to the induction of tolerance to allografts was recognized in the 1990s; however, their precise contribution to graft acceptance or rejection has not been elucidated. Recently, specialized populations of tissue-resident lymphocytes in nonlymphoid organs have been described...
November 14, 2017: Transplantation
https://www.readbyqxmd.com/read/29109728/invariant-natural-killer-t-cells-in-immune-regulation-of-blood-cancers-harnessing-their-potential-in-immunotherapies
#3
REVIEW
Pui Yeng Lam, Michael D Nissen, Stephen R Mattarollo
Invariant natural killer T (iNKT) cells are a unique innate T lymphocyte population that possess cytolytic properties and profound immunoregulatory activities. iNKT cells play an important role in the immune surveillance of blood cancers. They predominantly recognize glycolipid antigens presented on CD1d, but their activation and cytolytic activities are not confined to CD1d expressing cells. iNKT cell stimulation and subsequent production of immunomodulatory cytokines serve to enhance the overall antitumor immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29099628/murine-cd8-invariant-natural-killer-t-cells-are-negatively-selected-by-cd1d-expressed-on-thymic-epithelial-cells-and-dendritic-cells
#4
Sejin Oh, Hyunji Lee, Jung Hoon Shin, Changwan Hong, Se-Ho Park
BACKGROUND: CD1d-dependent invariant natural killer (iNKT) cells are found as either CD4 single positive (SP) or CD4/CD8 double negative (DN) cells in mice. The size of the CD8(+) iNKT population is extremely small. It is known that CD1d expression on developing thymocytes is sufficient for iNKT development and co-receptor choice, which is driven by Th-POK expression. This study aimed to examine the factors involved in the CD4/CD8 co-receptor choice of iNKT cells in addition to Th-POK-driven silencing of CD8 expression...
November 3, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/29097726/palmitate-inhibits-arthritis-by-inducing-t-bet-and-gata-3-mrna-degradation-in-inkt-cells-via-ire1%C3%AE-dependent-decay
#5
Jae Sung Ko, Jae Moon Koh, Jae-Seon So, Yoon Kyung Jeon, Hye Young Kim, Doo Hyun Chung
Long chain fatty acids (LCFAs) exert pro-inflammatory effects in vivo. However, little is known regarding the effect of LCFAs on invariant (i) NKT cell functions. Here, we report an inhibitory effect of saturated LCFAs on transcription factors in iNKT cells. Among the saturated LCFAs, palmitic acid (PA) specifically inhibited IL-4 and IFN-γ production and reduced gata-3 and t-bet transcript levels in iNKT cells during TCR-mediated activation. In iNKT cells, PA was localized and induced dilation in the endoplasmic reticulum and increased the mRNA levels of downstream molecules of IRE1α RNase...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29091327/unconventional-t-cells-in-chronic-hepatitis-b-patients-on-long-term-suppressive-therapy-with-tenofovir-followed-by-a-peg-ifn-add-on-strategy-a-randomized-study
#6
Elvira Stefania Cannizzo, Camilla Tincati, Francesca Binda, Paola Ronzi, Federico Angelo Cazzaniga, Spinello Antinori, Antonella d'Arminio Monforte, Giulia Marchetti, Laura Milazzo
HBV eradication in Chronic Hepatitis B (CHB) subjects is rarely achieved with either nucleos(t)ide analogues (NA) or pegylated interferon (Peg-IFN), which both have a limited effect in restoring immune responses. 30 CHB subjects on long-term treatment with tenofovir (TDF) and HBV suppression were enrolled and randomized 1:2 to either receive Peg-IFN-α-2a add-on therapy or continue TDF alone. We studied γδT and iNKT frequency and function (by flow cytometry) at baseline, at 12 weeks and 12 weeks after the end of treatment...
November 1, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29091262/isolation-and-functional-use-of-human-nkt-cells
#7
Mark A Exley, S Brian Wilson, Steven P Balk
This unit details methods for the isolation, in vitro expansion, and functional characterization of human iNKT cells. The term 'iNKT' derives from the fact that a large fraction of murine and some human NK marker+ T cells ('NKT') recognize the MHC class I-like CD1d protein and use an identical 'invariant' TCRα chain, which is generated in humans by precise Vα24 and Jα18 rearrangements with either no N-region diversity or subsequent trimming to identical or nearly identical amino acid sequence (hence, 'iNKT' cells)...
November 1, 2017: Current Protocols in Immunology
https://www.readbyqxmd.com/read/29091076/inkt-cells-require-tsc1-for-terminal-maturation-and-effector-lineage-fate-decisions
#8
Jinhong Wu, Jialong Yang, Kai Yang, Hongxia Wang, Balachandra Gorentla, Jinwook Shin, Yurong Qiu, Loretta G Que, W Michael Foster, Zhenwei Xia, Hongbo Chi, Xiao-Ping Zhong
No abstract text is available yet for this article.
November 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29083052/skewed-invariant-natural-killer-t-inkt-cells-impaired-inkt-b-cell-help-and-decreased-sap-expression-in-blood-lymphocytes-from-patients-with-common-variable-immunodeficiency
#9
L V Erazo-Borrás, J A Álvarez-Álvarez, C A Perez-Romero, J C Orrego-Arango, J L Franco-Restrepo, C M Trujillo-Vargas
Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analysed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B cell help. The total of iNKT cells was reduced in the PB of CVID patients, especially CD4+, CD4-/CD8- and CCR5+/CXCR3+...
September 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29073286/differential-adipokine-receptor-expression-on-circulating-leukocyte-subsets-in-lean-and-obese-children
#10
Genoveva Keustermans, Laila B van der Heijden, Berlinda Boer, Rianne Scholman, Roos Nuboer, Gerard Pasterkamp, Berent Prakken, Wilco de Jager, Eric Kalkhoven, Arieke J Janse, Henk S Schipper
BACKGROUND: Childhood obesity prevalence has increased worldwide and is an important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The production of inflammatory adipokines by obese adipose tissue contributes to the development of T2D and CVD. While levels of circulating adipokines such as adiponectin and leptin have been established in obese children and adults, the expression of adiponectin and leptin receptors on circulating immune cells can modulate adipokine signalling, but has not been studied so far...
2017: PloS One
https://www.readbyqxmd.com/read/29066547/role-of-granulocyte-macrophage-colony-stimulating-factor-production-by-t-cells-during-mycobacterium-tuberculosis-infection
#11
Alissa C Rothchild, Britni Stowell, Girija Goyal, Cláudio Nunes-Alves, Qianting Yang, Kadamba Papavinasasundaram, Christopher M Sassetti, Glenn Dranoff, Xinchun Chen, Jinhee Lee, Samuel M Behar
Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF(-/-)) are highly susceptible to infection with Mycobacterium tuberculosis, and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown...
October 24, 2017: MBio
https://www.readbyqxmd.com/read/29056249/nephrutix-a-randomized-double-blind-placebo-vs-rituximab-controlled-trial-assessing-t-cell-subset-changes-in-minimal-change-nephrotic-syndrome
#12
Ahmed Boumediene, Pauline Vachin, Kelhia Sendeyo, Julie Oniszczuk, Shao-Yu Zhang, Carole Henique-Greciet, Andre Pawlak, Vincent Audard, Mario Ollero, Vincent Guigonis, Djillali Sahali
Minimal-change nephrotic syndrome (MCNS) is an immune-mediated glomerular disease. We have analyzed the modifications on T-cell subsets in twenty-three patients who were highly steroid/calcineurin inhibitor and/or mycophenolate mofetil-dependent for frequently relapsing nephrotic syndrome (FRNS) and who were enrolled in a multicenter, double-blind, randomized, placebo vs Rituximab-controlled trial. Patients with FRNS entered the trial at remission and were randomly assigned to receive either Rituximab or placebo...
October 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29045904/inkt-cells-orchestrate-a-switch-from-inflammation-to-resolution-of-sterile-liver-injury
#13
Pei Xiong Liew, Woo-Yong Lee, Paul Kubes
After traumatic injury, some cells function as detectors to sense injury and to modulate the local immune response toward a restitution phase by affecting the local cytokine milieu. Using intravital microscopy, we observed that patrolling invariant natural killer T (iNKT) cells were initially excluded from a site of hepatic injury but subsequently were strategically arrested first via self-antigens and then by cytokines, circumscribing the injured site at exactly the location where monocytes co-localized and hepatocytes proliferated...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045892/wait-wait-%C3%A2-ok-now-go-in-inkt-cells-resolve-liver-inflammation
#14
Haiguang Wang, Kristin A Hogquist
Resolution of inflammation is pivotal to restoring tissue homeostasis, yet there is limited understanding of how this process is regulated. In this issue of Immunity, Liew et al. (2017) reveal a critical role for invariant natural killer T (iNKT) cells in switching inflammation to tissue repair in an interlukin-4-dependent process.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29018959/invariant-natural-killer-t-infiltration-in-neuroblastoma-with-favorable-outcome
#15
Tomoro Hishiki, Naoko Mise, Kazuaki Harada, Fumie Ihara, Mariko Takami, Takeshi Saito, Keita Terui, Mitsuyuki Nakata, Shugo Komatsu, Hideo Yoshida, Shinichiro Motohashi
BACKGROUND: Tumor immunity has been suggested to play a key role in clinical and biological behavior of neuroblastomas. Given that CD1-restricted invariant natural killer T (iNKT) cells enhance both innate and acquired tumor immunity, we investigated the expression of the iNKT-cell-specific T-cell receptor Vα24-Jα18 in neuroblastoma tissues and its correlation with clinical and biological characteristics. METHODS: Using real- time quantitative PCR, we quantified the expression of Vα24-Jα18 in untreated tumor samples from 107 neuroblastoma cases followed in our institution and analyzed the correlation between the presence of infiltrated iNKT cells and clinical characteristics or patients' outcome...
October 10, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/29018953/frequency-and-proliferative-response-of-circulating-invariant-natural-killer-t-cells-in-pediatric-patients-with-malignant-solid-tumors
#16
Tomoro Hishiki, Naoko Mise, Kazuaki Harada, Fumie Ihara, Mariko Takami, Takeshi Saito, Keita Terui, Mitsuyuki Nakata, Shugo Komatsu, Hideo Yoshida, Shinichiro Motohashi
BACKGROUND: Invariant natural killer T (iNKT) cells play an important role in tumor immunity, enhancing both innate and acquired immunity. We have previously shown the enhancement of antibody-dependent cellular cytotoxicity against neuroblastoma by activated iNKT cells. As a first step towards clinical application, we studied the frequency and proliferative response of circulating iNKT cells in children with and without cancer. METHODS: Blood samples were collected from 10 patients with pediatric malignant solid tumors and 11 patients with non-neoplastic diseases (control)...
October 10, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28986544/a-novel-mouse-model-of-inkt-cell-deficiency-generated-by-crispr-cas9-reveals-a-pathogenic-role-of-inkt-cells-in-metabolic-disease
#17
Yue Ren, Etsuko Sekine-Kondo, Risa Shibata, Megumi Kato-Itoh, Ayumi Umino, Ayaka Yanagida, Masashi Satoh, Komaki Inoue, Tomoyuki Yamaguchi, Keiichi Mochida, Susumu Nakae, Luc Van Kaer, Kazuya Iwabuchi, Hiromitsu Nakauchi, Hiroshi Watarai
iNKT cells play important roles in immune regulation by bridging the innate and acquired immune systems. The functions of iNKT cells have been investigated in mice lacking the Traj18 gene segment that were generated by traditional embryonic stem cell technology, but these animals contain a biased T cell receptor (TCR) repertoire that might affect immune responses. To circumvent this confounding factor, we have generated a new strain of iNKT cell-deficient mice by deleting the Traj18 locus using CRISPR/Cas9 technology, and these animals contain an unbiased TCR repertoire...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28986246/sphingosine-1-phosphate-alleviates-coxsackievirus-b3-induced-myocarditis-by-increasing-invariant-natural-killer-t-cells
#18
Xinggang Wang, Yong Yu, Minghui Li, Ying Yu, Guijian Liu, Yeqing Xie, Yuxi Liu, Xiangdong Yang, Yunzeng Zou, Junbo Ge, Ruizhen Chen
Sphingosine 1-phosphate (S1P), via binding to its specific receptors of S1PR1, participates in the regulation of both innate and adaptive immunity. Recent reports have identified S1P as a messenger mediating inflammation. However, roles of S1P in Coxsackievirus B3 (CVB3)-induced myocarditis were largely unknown. Here, we investigated the effect of S1P treatment on CVB3-induced myocarditis in vivo. We found that CVB3 infection downregulated S1PR1 expression in spleen and decreased the proportion of invariant natural killer T cells (iNKT) in CD3 positive T cells both in spleen and in blood from left ventricle, which accompanied by severe inflammation lesions and more virus capsid protein (VP1) expression in heart tissue...
October 3, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28980301/ly9-slamf3-receptor-differentially-regulates-inkt-cell-development-and-activation-in-mice
#19
Marta Cuenca, Joan Puñet-Ortiz, Maria Ruart, Cox Terhorst, Pablo Engel
Invariant natural killer T (iNKT) cells develop into three subsets (NKT1, NKT2, and NKT17) expressing a distinct transcription factor profile, which regulates cytokine secretion upon activation. iNKT cell development in the thymus is modulated by signaling lymphocytic activation molecule family (SLAMF) receptors. In contrast to other SLAMF members, Ly9 (SLAMF3) is a non-redundant negative regulator of iNKT cell development. Here, we show that Ly9 influences iNKT cell lineage differentiation. Ly9-deficient mice on a BALB/c background contained a significantly expanded population of thymic NKT2 cells, while NKT1 cells were nearly absent in BALB/c...
October 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28962035/immune-cell-and-transcriptomic-analysis-of-the-human-decidua-in-term-and-preterm-parturition
#20
S F Rinaldi, S Makieva, P T Saunders, A G Rossi, J E Norman
STUDY QUESTION: Is labour, both at term and preterm, associated with alterations in decidual lymphocyte densities and widespread changes to the decidual transcriptome? SUMMARY ANSWER: The onset of parturition, both at term and preterm, is associated with widespread gene expression changes in the decidua, many of which are related to inflammatory signalling, but is not associated with changes in the number of any of the decidual lymphocyte populations examined. WHAT IS KNOWN ALREADY: Given its location, directly at the maternal-foetal interface, the decidua is likely to play a pivotal role in the onset of parturition, however, the molecular events occurring in the decidua in association with the onset of labour, both at term and preterm, remain relatively poorly defined...
August 18, 2017: Molecular Human Reproduction
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