Deciphering the Role of microRNAs in Regulation of Immune Surveillance, Self-Tolerance and Allograft Transplant Outcome

2018 ◽  
Vol 13 (5) ◽  
pp. 336-344
Author(s):  
Cherry S. Leung ◽  
Song Lu ◽  
Jiatao Li ◽  
William KK Wu ◽  
Kathy O. Lui
Keyword(s):  
Immune Surveillance ◽  
Transplant Outcome ◽  
Self Tolerance

KIDNEY TRANSPLANTATION FROM MARGINAL DONORS. PREDICTIVE ROLE OF BIOPSY SCORE FOR LONG TERM GRAFT SURVIVAL AND TRANSPLANT OUTCOME

2008 ◽  
Vol 86 (Supplement) ◽  
pp. 582
Author(s):  
S Cristino ◽  
M P. Scolari ◽  
G La Manna ◽  
A Faenza ◽  
G Mosconi ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Transplant Outcome ◽  
Predictive Role ◽  
Marginal Donors ◽  
Biopsy Score

scholarly journals Induction of autoreactive B cells allows priming of autoreactive T cells.

1991 ◽  
Vol 173 (6) ◽  
pp. 1433-1439 ◽  
Author(s):  
R H Lin ◽  
M J Mamula ◽  
J A Hardin ◽  
C A Janeway
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cytochrome C ◽  
Autoantibody Production ◽  
Autoreactive T Cells ◽  
Human Cytochrome ◽  
Self Tolerance ◽  
Human Cytochrome C

A novel mechanism for breaking T cell self tolerance is described. B cells induced to make autoantibody by immunization of mice with the non-self protein human cytochrome c can present the self protein mouse cytochrome c to autoreactive T cells in immunogenic form. This mechanism of breaking T cell self tolerance could account for the role of foreign antigens in breaking not only B cell but also T cell self tolerance, leading to sustained autoantibody production in the absence of the foreign antigen.

scholarly journals Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Sadhak Sengupta ◽  
Jaclyn Marrinan ◽  
Caroline Frishman ◽  
Prakash Sampath
Keyword(s):  
Immune Response ◽  
Malignant Glioma ◽  
Dna Methyltransferase ◽  
Opportunistic Infections ◽  
Immune Surveillance ◽  
Drug Resistant ◽  
Methylguanine Dna Methyltransferase ◽  
Drug Resistant Mutation ◽  
Resistant Mutation

Malignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of surgical resection followed by radiation and temozolomide (TMZ) chemotherapy, concurrently with radiation and then as an adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and has added several months to the life expectancy of malignant glioma patients. However, TMZ is also responsible for inducing lymphopenia and myelosuppression in malignant glioma patients undergoing chemotherapy. Although TMZ-induced lymphopenia has been attributed to facilitate antitumor vaccination studies by inducing passive immune response, in general lymphopenic conditions have been associated with poor immune surveillance leading to opportunistic infections in glioma patients, as well as disrupting active antiglioma immune response by depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase (MGMT) activity, a DNA repair enzyme, by temozolomide has been determined to be the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been shown to render chemoprotection against TMZ. The immune modulating role of TMZ during glioma chemotherapy and possible mechanisms to establish a strong TMZ-resistant immune response have been discussed.

Adenosine A2AAgonist Administration Improves Islet Transplant Outcome: Evidence for the Role of Innate Immunity in Islet Graft Rejection

2010 ◽  
Vol 19 (5) ◽  
pp. 597-612 ◽  
Author(s):  
Preeti Chhabra ◽  
Kunjie Wang ◽  
Qiang Zeng ◽  
Mladen Jecmenica ◽  
Linda Langman ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Graft Rejection ◽  
Islet Graft ◽  
Transplant Outcome ◽  
Islet Transplant

scholarly journals A2B Adenosine Receptor and Cancer

2019 ◽  
Vol 20 (20) ◽  
pp. 5139 ◽  
Author(s):  
Zhan-Guo Gao ◽  
Kenneth A. Jacobson
Keyword(s):  
G Proteins ◽  
Anticancer Agents ◽  
Immune Suppression ◽  
Adenosine Receptors ◽  
Immune Surveillance ◽  
G Protein Coupled Receptors ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
G Protein Coupled

There are four subtypes of adenosine receptors (ARs), named A1, A2A, A2B and A3, all of which are G protein-coupled receptors (GPCRs). Locally produced adenosine is a suppressant in anti-tumor immune surveillance. The A2BAR, coupled to both Gαs and Gαi G proteins, is one of the several GPCRs that are expressed in a significantly higher level in certain cancer tissues, in comparison to adjacent normal tissues. There is growing evidence that the A2BAR plays an important role in tumor cell proliferation, angiogenesis, metastasis, and immune suppression. Thus, A2BAR antagonists are novel, potentially attractive anticancer agents. Several antagonists targeting A2BAR are currently in clinical trials for various types of cancers. In this review, we first describe the signaling, agonists, and antagonists of the A2BAR. We further discuss the role of the A2BAR in the progression of various cancers, and the rationale of using A2BAR antagonists in cancer therapy.

scholarly journals LANA and hnRNP A1 Regulate the Translation of LANA mRNA through G-Quadruplexes

2019 ◽  
Vol 94 (3) ◽  
Author(s):  
Prerna Dabral ◽  
Jay Babu ◽  
Andrew Zareie ◽  
Subhash C. Verma
Keyword(s):  
Viral Genome ◽  
Immune Surveillance ◽  
Class I ◽  
Nuclear Antigen ◽  
Host Immune System ◽  
Immune Recognition ◽  
Hnrnp A1 ◽  
Multifunctional Protein ◽  
G Quadruplex

ABSTRACT During the latent phase, Kaposi’s sarcoma-associated herpes virus (KSHV) maintains itself inside the host by escaping the host immune surveillance mechanism through restricted protein expression. Latency-associated nuclear antigen (LANA), the most abundantly expressed protein, is essential for viral persistence, as it plays important roles in latent viral DNA replication and efficient segregation of the viral genome to the daughter cells following cell division. KSHV evades immune detection by maintaining the levels of LANA protein below a threshold required for detection by the host immune system but sufficient to maintain the viral genome. LANA achieves this by controlling its expression through regulation of its promoters and by inhibiting its presentation through interaction with the proteins of class I and class II major histocompatibility complex (MHC) pathways. In this study, we identified a mechanism of LANA expression and restricted immune recognition through formation of G-quadruplexes in LANA mRNA. We show that the formation of these stable structures in LANA mRNA inhibits its translation to control antigen presentation, which was supported by treatment of cells with TMPyP4, a G-quadruplex-stabilizing ligand. We identified heterogenous ribonucleoprotein A1 (hnRNP A1) as a G-quadruplex-unwinding helicase, which unfolds these stable secondary structures to regulate LANA translation. IMPORTANCE LANA, the most abundantly expressed protein during latency, is a multifunctional protein which is absolutely required for the persistence of KSHV in the host cell. Even though the functions of LANA in aiding pathogenesis of the virus have been extensively studied, the mechanism of how LANA escapes host’s immune surveillance is not fully understood. This study sheds light on the autoregulatory role of LANA to modulate its expression and immune evasion through formation of G-quadruplexes in its mRNA. We used G-quadruplex-stabilizing ligand to define the inhibition in LANA expression and presentation on the cell surface through MHC class I. We defined the autoregulatory role of LANA and identified a cellular RNA helicase, hnRNP A1, regulating the translation of LANA mRNA. This interaction of hnRNP A1 with LANA mRNA could be exploited for controlling KSHV latency.

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