A retinoic acid--rich tumor microenvironment provides clonal survival cues for tumor-specific CD8(+) T cells.
AuthorsGuo Y, Pino-Lagos K, Ahonen CA, Bennett KA, Wang J, Napoli JL, Blomhoff R, Sockanathan S, Chandraratna RA, Dmitrovsky E, Turk MJ, Noelle RJ,
JournalCancer Res
PubMed ID22902413
While vitamin A has been implicated in host resistance to infectious disease, little is known about the role of vitamin A and its active metabolite, retinoic acid (RA) in host defenses against cancer. Here, we show that local RA production within the tumor microenvironment (TME) is increased up to 5-fold ... More
Establishment and characterization of a sustained delayed-type hypersensitivity model with arthritic manifestations in C57BL/6J mice.
'Rheumatoid arthritis (RA) is a chronic progressive, inflammatory and destructive autoimmune disease, characterised by synovial joint inflammation and bone erosion. To better understand the pathophysiology and underlying immune mechanisms of RA various models of arthritis have been developed in different inbred strains of mice. Establishment of arthritis models with components ... More
IL-2-dependent adaptive control of NK cell homeostasis.
AuthorsGasteiger G, Hemmers S, Bos PD, Sun JC, Rudensky AY
JournalJ Exp Med
PubMed ID23650439
'Activation and expansion of T and B lymphocytes and myeloid cells are controlled by Foxp3(+) regulatory T cells (T reg cells), and their deficiency results in a fatal lympho- and myeloproliferative syndrome. A role for T reg cells in the homeostasis of innate lymphocyte lineages remained unknown. Here, we report ... More
Comparative analysis of simian immunodeficiency virus gag-specific effector and memory CD8+ T cells induced by different adenovirus vectors.
AuthorsTan WG, Jin HT, West EE, Penaloza-MacMaster P, Wieland A, Zilliox MJ, McElrath MJ, Barouch DH, Ahmed R,
JournalJ Virol
PubMed ID23175355
'Adenovirus (Ad) vectors are widely used as experimental vaccines against several infectious diseases, but the magnitude, phenotype, and functionality of CD8(+) T cell responses induced by different adenovirus serotypes have not been compared. To address this question, we have analyzed simian immunodeficiency virus Gag-specific CD8(+) T cell responses in mice ... More
The novel BCR-ABL and FLT3 inhibitor ponatinib is a potent inhibitor of the MDR-associated ATP-binding cassette transporter ABCG2.
'Ponatinib is a novel tyrosine kinase inhibitor with potent activity against BCR-ABL with mutations, including T315I, and also against fms-like tyrosine kinase 3. We tested interactions between ponatinib at pharmacologically relevant concentrations of 50 to 200 nmol/L and the MDR-associated ATP-binding cassette (ABC) proteins ABCB1, ABCC1, and ABCG2. Ponatinib enhanced ... More
Adenosine stimulates the migration of human endothelial progenitor cells. Role of CXCR4 and microRNA-150.
AuthorsRolland-Turner M, Goretti E, Bousquenaud M, Léonard F, Nicolas C, Zhang L, Maskali F, Marie PY, Devaux Y, Wagner D
JournalPLoS One
PubMed ID23326587
Administration of endothelial progenitor cells (EPC) represents a promising option to regenerate the heart after myocardial infarction, but is limited because of low recruitment and engraftment in the myocardium. Mobilization and migration of EPC are mainly controlled by stromal cell-derived factor 1a (SDF-1a) and its receptor CXCR4. We hypothesized that ... More
Retinoic acid hypersensitivity promotes peripheral tolerance in recent thymic emigrants.
AuthorsBhaumik S, Giffon T, Bolinger D, Kirkman R, Lewis DB, Weaver CT, Randolph DA,
JournalJ Immunol
PubMed ID23401586
Whereas thymic education eliminates most self-reactive T cells, additional mechanisms to promote tolerance in the periphery are critical to prevent excessive immune responses against benign environmental Ags and some self-Ags. In this study we show that murine CD4(+) recent thymic emigrants (RTEs) are programmed to facilitate tolerance in the periphery. ... More
The effects of 5-azacytidine on the function and number of regulatory T cells and T-effectors in myelodysplastic syndrome.
AuthorsCostantini B, Kordasti SY, Kulasekararaj AG, Jiang J, Seidl T, Abellan PP, Mohamedali A, Thomas NS, Farzaneh F, Mufti GJ,
JournalHaematologica
PubMed ID23242597
Expansion of regulatory T cells occurs in high-risk myelodysplastic syndrome and correlates with a poor prognosis. DNA methyltransferase inhibitors, particularly 5-azacytidine, have been shown to increase the survival of patients with high-risk myelodysplastic syndrome. It is not entirely clear whether this improvement in patients' survival is related to the effects ... More
Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation.
AuthorsWu T, Wieland A, Araki K, Davis CW, Ye L, Hale JS, Ahmed R,
JournalProc Natl Acad Sci U S A
PubMed ID22665768
MicroRNAs are important regulators of various developmental and physiological processes. However, their roles in the CD8(+) T-cell response are not well understood. Using an acute viral infection model, we show that microRNAs of the miR-17-92 cluster are strongly induced after T-cell activation, down-regulated after clonal expansion, and further silenced during ... More
Inhibition of the Kit ligand/c-Kit axis attenuates metastasis in a mouse model mimicking local breast cancer relapse after radiotherapy.
Local breast cancer relapse after breast-saving surgery and radiotherapy is associated with increased risk of distant metastasis formation. The mechanisms involved remain largely elusive. We used the well-characterized 4T1 syngeneic, orthotopic breast cancer model to identify novel mechanisms of postradiation metastasis. 4T1 cells were injected in 20 Gy preirradiated mammary ... More
Binder of sperm 1 and epididymal sperm binding protein 1 are associated with different bull sperm subpopulations.
Previously, we showed that binder of sperm 1 (BSP1) and epididymal sperm binding protein 1 (ELSPBP1) proteins are more abundant in the immotile bovine sperm subpopulation following cryopreservation. In this study, we investigated the association of BSP1 and ELSPBP1 with sperm in relation to their ability to survive the cryopreservation ... More
Tetrahydrobiopterin deficiency and nitric oxide synthase uncoupling contribute to atherosclerosis induced by disturbed flow.
AuthorsLi L, Chen W, Rezvan A, Jo H, Harrison DG,
JournalArterioscler Thromb Vasc Biol
PubMed ID21512164
Tetrahydrobiopterin (BH(4)) is a critical cofactor for nitric oxide (NO) synthesis by NO synthase (NOS). Recently, we demonstrated that disturbed flow produced by partial carotid ligation decreases BH(4) levels in vivo. We therefore aimed to determine whether atherosclerosis induced by disturbed flow is due to BH(4) deficiency and NOS uncoupling ... More
Stability screening of arrays of major histocompatibility complexes on combinatorially encoded flow cytometry beads.
AuthorsChew SL, Or MY, Chang CX, Gehring AJ, Bertoletti A, Grotenbreg GM,
JournalJ Biol Chem
PubMed ID21680737
The binding and stabilization capacity of potential T cell epitopes to class I MHC molecules form the basis for their immunogenicity and provide fundamental insight into factors that dictate cellular immune responses. We have developed a versatile high throughput cell-free method to measure MHC stability by capturing a variety of ... More
Regulation of IL-17A production is distinct from IL-17F in a primary human cell co-culture model of T cell-mediated B cell activation.
AuthorsMelton AC, Melrose J, Alajoki L, Privat S, Cho H, Brown N, Plavec AM, Nguyen D, Johnston ED, Yang J, Polokoff MA, Plavec I, Berg EL, O'Mahony A
JournalPLoS One
PubMed ID23505568
Improper regulation of B cell responses leads to excessive production of antibodies and contributes to the development of autoimmune disease. T helper 17 (Th17) cells also drive the development of autoimmune disease, but the role of B cells in shaping Th17 cell-mediated immune responses, as well as the reciprocal regulation ... More
Epididymosomes transfer epididymal sperm binding protein 1 (ELSPBP1) to dead spermatozoa during epididymal transit in bovine.
AuthorsD'Amours O, Frenette G, Bordeleau LJ, Allard N, Leclerc P, Blondin P, Sullivan R
JournalBiol Reprod
PubMed ID22875906
Previously, we showed that epididymal sperm binding protein 1 (ELSPBP1) characterizes spermatozoa already dead before ejaculation in bovine. In this study, we investigated the presence of ELSPBP1 in bull genital tract as well as its acquisition by spermatozoa during epididymal transit. As assessed by real-time RT-PCR, ELSPBP1 was highly expressed ... More
Restricted replication of xenotropic murine leukemia virus-related virus in pigtailed macaques.
AuthorsDel Prete GQ, Kearney MF, Spindler J, Wiegand A, Chertova E, Roser JD, Estes JD, Hao XP, Trubey CM, Lara A, Lee K, Chaipan C, Bess JW, Nagashima K, Keele BF, Macallister R, Smedley J, Pathak VK, Kewalramani VN, Coffin JM, Lifson JD
JournalJ Virol
PubMed ID22238316
Although xenotropic murine leukemia virus-related virus (XMRV) has been previously linked to prostate cancer and myalgic encephalomyelitis/chronic fatigue syndrome, recent data indicate that results interpreted as evidence of human XMRV infection reflect laboratory contamination rather than authentic in vivo infection. Nevertheless, XMRV is a retrovirus of undefined pathogenic potential that ... More