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Jahnavi Aluri, Maya Gupta, Aparna Dalvi, Snehal Mhatre, Manasi Kulkarni, Gouri Hule, Mukesh Desai, Nitin Shah, Prasad Taur, Ramprasad Vedam, Manisha Madkaikar
Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy available for treating these patients...
2018: Frontiers in Immunology
Yi-Ping Jin, Nicole M Valenzuela, Xiaohai Zhang, Enrique Rozengurt, Elaine F Reed
Transplant recipients developing donor-specific HLA class II (HLA-II) Abs are at higher risk for Ab-mediated rejection (AMR) and transplant vasculopathy. To understand how HLA-II Abs cause AMR and transplant vasculopathy, we determined the signaling events triggered in vascular endothelial cells (EC) following Ab ligation of HLA-II molecules. HLA-II expression in EC was induced by adenoviral vector expression of CIITA or by pretreatment with TNF-α/IFN-γ. Ab ligation of class II stimulated EC proliferation and migration...
February 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Massimiliano Bissa, Greta Forlani, Carlo Zanotto, Giovanna Tosi, Carlo De Giuli Morghen, Roberto S Accolla, Antonia Radaelli
A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+ T cells. In this context, the class II transactivator (CIITA) has a pivotal role in triggering the adaptive immune response through induction of the expression of class-II major histocompatibility complex molecule (MHC-II), that can present antigens to CD4+ T helper cells...
2018: PloS One
Karim L Kreft, Gijsbert P Van Nierop, Sandra M J Scherbeijn, Malou Janssen, Georges M G M Verjans, Rogier Q Hintzen
Objective: To assess whether MS genetic risk polymorphisms (single nucleotide polymorphism [SNP]) contribute to the enhanced humoral immune response against Epstein-Barr virus (EBV) infection in patients with MS. Methods: Serum anti-EBV nuclear antigen 1 (EBNA-1) and early antigen D (EA-D) immunoglobulin γ (IgG) levels were quantitatively determined in 668 genotyped patients with MS and 147 healthy controls. Anti-varicella-zoster virus (VZV) IgG levels were used as a highly prevalent, non-MS-associated control herpesvirus...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
Jeremy Forsberg, Xinge Li, Birce Akpinar, Roger Salvatori, Martin Ott, Boris Zhivotovsky, Magnus Olsson
Despite recent achievements implicating caspase-2 in tumor suppression, the enzyme stands out from the apoptotic caspase family as a factor whose function requires further clarification. To specify enzyme characteristics through the definition of interacting proteins in apoptotic or non-apoptotic settings, a yeast 2-hybrid (Y2H) screen was performed using the full-length protein as bait. The current report describes the analysis of a captured prey and putative novel caspase-2 interacting factor, the regulatory factor X-associated ankyrin-containing protein (RFXANK), previously associated with CIITA, the transactivator regulating cell-type specificity and inducibility of MHC class II gene expression...
January 23, 2018: Cell Death & Disease
Charlotte Girard-Guyonvarc'h, Jennifer Palomo, Praxedis Martin, Emiliana Rodriguez, Sabina Troccaz, Gaby Palmer, Cem Gabay
The term macrophage activation syndrome (MAS) defines a severe, potentially fatal disorder characterized by overwhelming inflammation and multiorgan involvement. Interleukin (IL)-18 is a pro-inflammatory cytokine belonging to the IL-1 family, the activity of which is regulated by its endogenous inhibitor IL-18 binding protein (IL-18BP). Elevated IL-18 levels have been reported in patients with MAS. Herein we show that upon repeated toll-like receptor (TLR)9 stimulation with CpG, IL-18BP-/- mice display severe MAS manifestations, including increased weight loss, splenomegaly, anemia, thrombocytopenia, hyperferritinemia and bone marrow hemophagocytosis as compared to wild-type mice...
January 2, 2018: Blood
David D W Twa, Anja Mottok, Kerry J Savage, Christian Steidl
Primary testicular lymphomas (PTL) are the most prevalent type of testicular cancer arising in men over the age of 60. PTL accounts for approximately 1-2% of all non-Hodgkin lymphomas and most present with localized disease but despite this, outcome is poor. The majority of cases represent an extranodal manifestation of diffuse large B-cell lymphoma (DLBCL), known as primary testicular DLBCL (PT-DLBCL). Gene expression profiling has established that over 75% of PT-DLBCLs resemble the activated B-cell-like (ABC) or non-germinal center subtype of nodal DLBCL...
December 20, 2017: Blood Reviews
John M Yavorski, George Blanck
The role of tumor cell expression of major histocompatibility class II (MHCII) has been controversial, with evidence indicating that tumor cell expression of MHCII may lead to an anti-tumor immune response and to tumor cell apoptosis and that MHCII has pro-tumorigenic functions. The cancer genome atlas (TCGA) indicates numerous deleterious mutations for the highly specific, MHCII transcriptional activation proteins, RFX5, RFXAP, RFXANK and CIITA. Also, mutations in the non-polymorphic, human leukocyte antigen (HLA)-DRA gene, which encodes the heavy chain for the most prominent human MHCII molecule, HLA-DR, are common...
December 2017: Molecular and Clinical Oncology
Jing-Bo Yang, Zhi-Bin Zhao, Qing-Zhi Liu, Tai-Dou Hu, Jie Long, Kai Yan, Zhe-Xiong Lian
Macrophages are a critical component in host immune responses against tumor. In this work we investigated the role of forkhead box O1 (FoxO1) in the transcriptional regulation in macrophages, which affects the anti-tumor functions of tumor-associated macrophages (TAMs). First, we showed that TAMs expressed reduced levels of FoxO1, which was associated with their protumoral M2 polarization state. The suppression of FoxO1 expression in TAM was induced by the hypoxic condition in the tumor microenviroment. Next, we confirmed that FoxO1 positively regulates MHC-II genes by binding to the promoter region of Ciita gene, the master activator of multiple MHC-II genes...
December 14, 2017: Oncogene
Bi Shi, Aaron J Thomas, Abby D Benninghoff, Benjamin R Sessions, Qinggang Meng, Parveen Parasar, Heloisa M Rutigliano, Kenneth L White, Christopher J Davies
PROBLEM: The regulatory mechanisms governing differential expression of classical major histocompatibility complex (MHC) class I (MHC-Ia) and non-classical MHC class I (MHC-Ib) genes are poorly understood. METHOD OF STUDY: Quantitative reverse transcription- polymerase chain reaction (PCR) was used to compare the abundance of MHC-I transcripts and related transcription factors in peripheral blood mononuclear cells (PBMC) and placental trophoblast cells (PTC). Methylation of MHC-I CpG islands was detected by bisulfite treatment and next-generation sequencing...
January 2018: American Journal of Reproductive Immunology: AJRI
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
Rong Li, Mengjiao Guo, Jing Lin, Tongjie Chai, Liangmeng Wei
[This corrects the article on p. 1629 in vol. 8, PMID: 28878764.].
2017: Frontiers in Microbiology
Hassan Muhammad Yankuzo, Yusha'u Shu'aibu Baraya, Zulkarnain Mustapha, Kah Keng Wong, Nik Soriani Yaacob
ETHNOPHARMACOLOGICAL RELEVANCE: Strobilanthes crispus Blume is traditionally consumed among local Malay and indigenous communities for the treatment of cancer and other ailments such as gastrointestinal disorders, inflammatory wounds of snake bite and immune system activation amongst others. We previously demonstrated that a bioactive fraction of S. crispus leaves (F3) was cytotoxic to breast cancer cells in vitro and inhibited tumor growth in N-methyl-N-nitrosourea (NMU)-induced breast cancer rat model...
March 1, 2018: Journal of Ethnopharmacology
Greta Forlani, Roberto S Accolla
Coevolution of the three basic mechanisms of immunity, intrinsic, innate and adaptive, is a constant feature of the host defense against pathogens. Within this frame, a peculiar role is played by restriction factors (RFs), elements of intrinsic immunity that interfere with viral life cycle. Often considered as molecules whose specific functions are distinct and unrelated among themselves recent results indicate instead, at least for some of them, a concerted action against the pathogen. Here we review recent findings on the antiviral activity of tripartite motif 22 (TRIM22) and class II transactivator (CIITA), first discovered as human immunodeficiency virus 1 RFs, but endowed with general antiviral activity...
2017: Frontiers in Immunology
Grzegorz Pietz, Rituparna De, Maria Hedberg, Veronika Sjöberg, Olof Sandström, Olle Hernell, Sten Hammarström, Marie-Louise Hammarström
BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria. METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels...
2017: PloS One
Yadav Sapkota, Immaculata De Vivo, Valgerdur Steinthorsdottir, Amelie Fassbender, Lisa Bowdler, Julie E Buring, Todd L Edwards, Sarah Jones, Dorien O, Daniëlle Peterse, Kathryn M Rexrode, Paul M Ridker, Andrew J Schork, Gudmar Thorleifsson, Leanne M Wallace, Peter Kraft, Andrew P Morris, Dale R Nyholt, Digna R Velez Edwards, Mette Nyegaard, Thomas D'Hooghe, Daniel I Chasman, Kari Stefansson, Stacey A Missmer, Grant W Montgomery
Genome-wide association (GWA) studies have identified 19 independent common risk loci for endometriosis. Most of the GWA variants are non-coding and the genes responsible for the association signals have not been identified. Herein, we aimed to assess the potential role of protein-modifying variants in endometriosis using exome-array genotyping in 7164 cases and 21005 controls, and a replication set of 1840 cases and 129016 controls of European ancestry. Results in the discovery sample identified significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and gene-level (CIITA and PARP4) meta-analyses, but these did not survive replication...
September 12, 2017: Scientific Reports
Rong Li, Mengjiao Guo, Jing Lin, Tongjie Chai, Liangmeng Wei
Class II major histocompatibility complex (MHC-II) transactivator (CIITA) is a member of the pattern recognition receptor in cytoplasm, which is involved in host innate immune responses. In this study, the full-length cDNA of Cherry Valley duck CIITA (duCIITA) was cloned from the spleen of healthy Cherry Valley ducks for the first time. The CDs of duCIITA have 3648 bp and encode 1215 amino acids. The homology analysis of CIITAs amino acid sequence showed that the duCIITA has the highest identity with the Anas platyrhynchos (94...
2017: Frontiers in Microbiology
Joseph M Ladowski, Luz M Reyes, Gregory R Martens, James R Butler, Zheng-Yu Wang, Devin E Eckhoff, Matt Tector, A Joseph Tector
BACKGROUND: Over 130 000 patients in the United States alone need a life-saving organ transplant. Genetically modified porcine organs could resolve the donor organ shortage, but human xenoreactive antibodies destroy pig cells and are the major barrier to clinical application of xenotransplantation. The objective of this study was to determine whether waitlisted patients possess preformed antibodies to swine leukocyte antigen (SLA) class II, homologs of the class II human leukocyte antigens (HLA)...
August 24, 2017: Transplantation
Quang Mather, Jonathon Priego, Kristi Ward, Verma Kundan, Dat Tran, Alok Dwivedi, Brad A Bryan
Benign lipomas and well-differentiated liposarcomas share many histological and molecular features. Due to their similarities, patients with these lipomatous tumors are misdiagnosed up to 40% of the time following radiological detection, up to 17% of the time following histological examination, and in as many as 15% of cases following fluorescent in situ hybridization for chromosomal anomalies. Incorrect classification of these two tumor types leads to increased costs to the patient and delayed accurate diagnoses...
September 2017: Molecular and Clinical Oncology
Heather M Evans, Andrew Simpson, Shu Shen, Arnold J Stromberg, Carol L Pickett, Beth A Garvy
The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan...
October 2017: Infection and Immunity
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