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We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.
Mixing up immune memory
The immune system’s keen memory is key to long-lasting immunity in response to infections and vaccinations. Once activated by a pathogen, the immune system’s T cells divide and differentiate into several different “mature” cell types, including memory T cells that “remember” previously encountered pathogens and help boost the immune response to them and T helper (Th) cells that regulate the immune response. Commitment to a particular Th cell lineage had been thought to be irreversible.
Mark Boothby, M.D., Ph.D., and colleagues recently developed evidence challenging this rule. In the July 8 Proceedings of the National Academy of Sciences, they show that T cells that have become committed Th type 2 cells maintain the ability to differentiate further after spending time as memory-type cells. As expected, these memory cells, when re-activated, could turn their Th2-type program back on. But contrary to previous assumptions, the same cells could also produce Th1-type inflammatory chemicals (cytokines such as interferon gamma). This unexpected flexibility, the authors suggest, may play an important role in anti-viral, anti-tumor and allergic responses.
— Melissa Marino
Sight-stealing protein
Glaucoma, a leading cause of visual impairment and blindness, is a complex set of diseases with elevated intraocular pressure as a risk factor. A search for genes with altered expression in glaucoma has turned up multiple candidates that may contribute to disease pathology. Rachel Kuchtey, M.D., Ph.D., and colleagues have investigated the protein angiopoietin-like 7 (ANGPTL7).
They found that glaucoma stimuli (steroids and growth factors) increase ANGPTL7 secretion by cultured trabecular meshwork cells – cells that are involved in setting the intraocular pressure. ANGPTL7 was elevated in aqueous humor – the fluid between the lens and the cornea – from patients with glaucoma, and ANGPTL7 concentrations increased with disease progression in an animal model of glaucoma. The team also showed that cultured cells overexpressing ANGPTL7 produce more collagen, a potential mechanism for glaucoma pathogenesis. The findings in the August Investigative Ophthalmology & Visual Science support a pathologic role in glaucoma for ANGPTL7 and suggest it may be a useful therapeutic target.
— Leigh MacMillan
Biological ‘bandage’ for wounds
Wounds that won’t heal cause chronic discomfort and suffering for more than 7 million people worldwide. Lillian Nanney, Ph.D., and colleagues are exploring potential therapies to aid wound healing. In the September issue of the American Journal of Pathology, the researchers report that calreticulin, a protein normally found inside the body’s cells, stimulates wound repair in an animal model that mimics human skin healing.
They found that applying calreticulin to partial-thickness injuries allowed wounds to heal faster than wounds treated with the only available drug on the market. The treatment also facilitated wound healing in an animal model of impaired healing (as often seen in people with underlying conditions like diabetes). While investigating calreticulin’s healing mechanisms, the researchers found increased levels of TGF-beta3, a key regulator of wound healing, in calreticulin-treated wounds and increased proliferation and migration in three types of cultured skin cells. The results highlight the significant and multicellular roles for calreticulin in wound repair, suggesting that the compound could be a beneficial therapeutic for treating chronic non-healing wounds.
— Melissa Marino
Immune cells turn foe, promote cancer
Dendritic cells (DCs) – named for their branched projections – are important regulators of the immune response. The microenvironment of solid tumors, which includes high concentrations of the chemical adenosine, can affect the maturation of DCs, converting them from a protective to a pathologic factor.
Mikhail Dikov, Ph.D., Igor Feoktistov, M.D., Ph.D., and colleagues explored the role of adenosine on DC maturation from mouse and human precursor cells. They report in the Sept. 1 issue of Blood that adenosine works through its A2B receptor to induce the generation of a distinct subset of DCs, which – unlike normal DCs – produce factors that promote blood vessel and tumor growth and suppress the anti-tumor immune response. The team further demonstrates – in the September issue of Neoplasia – that mouse lung cancer cells promote their own growth through an A2B receptor-dependent signaling pathway in host immune cells. Together, the studies suggest that the A2B adenosine receptor may be a valuable therapeutic target for cancer.
— Leigh MacMillan
Past Aliquots
June 22, 2012
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April 27, 2012
April 13, 2012
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March 16, 2012