Posts Tagged Immune System

Discovery of new white blood cell reveals target for better vaccine design


ScienceDaily (July 27, 2012) — Researchers in Newcastle and Singapore have identified a new type of white blood cell which activates a killing immune response to an external source — providing a new potential target for vaccines for conditions such as cancer or Hepatitis B.

Publishing in the journal Immunity, the team of researchers from Newcastle University in collaboration with A*STAR’s Singapore Immunology Network (SIgN) describe a new human tissue dendritic cell with cross-presenting function.

Dendritic cells (DCs) are a type of white blood cell that orchestrate our body’s immune responses to infectious agents such as bacteria and viruses, as well as cancer cells. They are also very important for eliciting the immune response generated by vaccines.

DCs kick start an immune response by presenting small fragments of molecules from micro-organisms such as bacteria and viruses, or from vaccines or tumours, called antigens on their surface. This leads to activation of another white blood cell subset called T cells, which specialise in killing cells and are crucial for eliminating cancerous or infected cells. Most cells are only able to present antigens from within themselves, and so will only elicit an immune response if they are infected themselves. Only a specialised subset of DCs is able to generate a response to an external source of antigen, for example bacteria, vaccines and tumours.

The identity of human tissue DCs that are capable of presenting external antigen to activate the cell-killing response by T cells — a process termed ‘cross-presentation’ — has remained a mystery. Their discovery, as revealed by this research, will help scientists to design better targeted vaccine strategies to treat cancer and infections such as Hepatitis B.

“These are the cells we need to be targeting for anti-cancer vaccines,” said Dr Muzlifah Haniffa, a Wellcome Trust Intermediate Fellow and Senior Clinical Lecturer at Newcastle University. “Our discovery offers an accessible, easily targetable system which makes the most of the natural ability of the cell.” The researchers also showed for the first time that dendritic cell subsets are conserved between species and have in effect created a map, facilitating the translation of mouse studies to the human immune system.

“The cross-species map is in effect a Rosetta stone that deciphers the language of mouse into human,” explains Matthew Collin, Professor of Haematology from Newcastle University.

In the paper the researchers describe how the cross-presenting DCs were first isolated from surplus plastic surgery skin which was digested to melt the gelatinous collagen to isolate the cells. This research will have significant impact on the design of vaccines and other targeted immunotherapies.

The Rosetta Stone of our immune system: Mapping Human and Mouse dendritic cells

The Newcastle University team in collaboration with A*STAR’s Singapore Immunology Network (SIgN) have for the first time ever aligned the dendritic cell subsets between mouse and humans allowing the accurate translation of mouse studies into the human model for the first time.

The researchers isolated the dendritic cells from human blood and skin and those from mouse blood, lung and liver. Using gene expression analysis, they identified gene signatures for each human dendritic cell subset. Mouse orthologues of these genes were identified and a computational analysis was performed to match subsets across species.

This provides scientists for the first time with an accurate model to compare DCs between species. Professor Matthew Collin explains: “This is in effect a Rosetta stone that deciphers the language of mouse into human. It can put into context the findings from the extensive literature using mouse models to the human settings.”

Dr. Haniffa added: “These gene signatures are available in a public repository accessible for all researchers to benefit from the data. It will allow detailed knowledge of individual human dendritic cell subsets to enable specific targeting of these cells for therapeutic strategy.”

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The above story is reprinted from materials provided by Newcastle University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Muzlifah Haniffa, Amanda Shin, Venetia Bigley, Naomi McGovern, Pearline Teo, Peter See, Pavandip Singh Wasan, Xiao-Nong Wang, Frano Malinarich, Benoit Malleret, Anis Larbi, Pearlie Tan, Helen Zhao, Michael Poidinger, Sarah Pagan, Sharon Cookson, Rachel Dickinson, Ian Dimmick, Ruth F. Jarrett, Laurent Renia, John Tam, Colin Song, John Connolly, Jerry K.Y. Chan, Adam Gehring, Antonio Bertoletti, Matthew Collin, Florent Ginhoux. Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103 Nonlymphoid Dendritic Cells. Immunity, 2012; 37 (1): 60 DOI: 10.1016/j.immuni.2012.04.012

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Novel therapy may prevent damage to the retina in diabetic eye diseases


ScienceDaily (July 27, 2012) — Researchers at the University of Michigan Kellogg Eye Center have identified a compound that could interrupt the chain of events that cause damage to the retina in diabetic retinopathy. The finding is significant because it could lead to a novel therapy that targets two mechanisms at the root of the disease: inflammation and the weakening of the blood barrier that protects the retina.

To date, treatments for diabetic retinopathy, the leading cause of blindness among working-age Americans, have been aimed largely at one of those mechanisms.

In diabetic retinopathy, damage to the retina results, in part, from the activity of vascular endothelial growth factor (VEGF), a protein that weakens the protective blood-retinal barrier. Recent drugs targeting VEGF have exhibited good response for nearly half of the patients with diabetic retinopathy. But researchers believe that there is also an inflammatory component that may contribute to the disease process.

The study, published in the Biochemical Journal, June 2012 [epub ahead of print] identifies a specific protein common to both pathways as an important target in regulating the disease process in which blood vessels become leaky, and provides a drug that may be developed into a therapeutic intervention for patients in which anti-VEGF treatment alone is not sufficient.

“In diabetic retinopathy and a host of other retinal diseases, increases in VEGF and inflammatory factors — some of the same factors that contribute to the response to an infection — cause blood vessels in the eye to leak which, in turn, results in a buildup of fluid in the neural tissue of the retina,” says David A. Antonetti, Ph.D., Professor, Department of Ophthalmology and Visual Sciences and Molecular and Integrative Physiology, who has also been awarded a Jules and Doris Stein Professorship from Research to Prevent Blindness. “This insidious form of modified inflammation can eventually lead to blindness.”

The compound targets atypical protein kinase C (aPKC), required for VEGF to make blood vessels leak. Moreover, Antonetti’s laboratory has demonstrated that the compound is effective at blocking damage from tumor necrosis factor also elevated in diabetic retinopathy that comprises part of the inflammation. Benefits of this compound could extend to therapies for uveitis, or changes to the brain blood vessels in the presence of brain tumors or stroke.

“This is a great leap forward,” says Antonetti. “We’ve identified an important target in regulating blood vessel leakage in the eye and we have a therapy that works in animal models. Our research is in the early stages of development. We still have a long way to go to demonstrate effectiveness of this compound in humans to create a new therapy but the results are very promising.”

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The above story is reprinted from materials provided by University of Michigan Health System, via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Paul Titchenell, Cheng-Mao Lin, Jason Keil, Jeffrey Sundstrom, Charles Smith, David Antonetti. Novel Atypical PKC Inhibitors Prevent Vascular Endothelial Growth Factor-Induced Blood-Retinal Barrier Dysfunction. Biochemical Journal, 2012; DOI: 10.1042/BJ20111961

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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