Selectively dampening harmful immune responses

A misdirected immune response can lead to allergies, autoimmune diseases and rejection of transplant organs and therapeutic drugs. Currently available immune suppressants have major drawbacks, but researchers from The Scripps Research Institute (TSRI) have demonstrated a new technique to selectively repress unwanted immune reactions without disabling the immune system altogether.

The study focused on a problem faced by some hemophiliacs – rejection of a therapeutic replacement for the blood clotting protein Factor VIII. Without enough Factor VIII, patients risk potentially fatal, uncontrolled bleeding.  But 20 to 30 percent of hemophiliacs produce an immune system attack against replacement Factor VIII, rendering it ineffective as a treatment.

In developing a new immune-suppression method scientists drew upon their knowledge of apoptosis (programmed cell death) triggered when certain molecules bind to the surface of B-cells (disease fighting leukocytes produced in bone marrow).

Mice genetically altered to lack Factor VIII were treated with nanoparticles that included both Factor VIII and a glycan (type of sugar) that binds to a key B-cell receptor.  This combination selectively induced apoptosis only in troublesome B-cells thus preventing Factor VIII rejection without disabling the rest of the immune system.

—Findings appear in the Journal of Clinical Investigation. News release at http://bit.ly/11zYjpU


Previously unknown role in activating T cells

Researchers at the La Jolla Institute for Allergy and Immunology reveal a surprising finding about the intricate pathway involved in turning on T cells. This involves the role of the septin protein in the calcium response, essential for immune cells activation.

The discovery builds on earlier work by the same researchers on the formation of calcium channel pores.  Understanding the channel’s entryway is one of the most sought after mysteries in biomedical science because it is the gateway to T cell function in fighting disease.  T-cells are leukocytes produced in bone marrow that then mature in the thymus (hence their “T” designation).

Heretofore, researchers knew that septins existed in the cellular surface membrane – where they build scaffolding to provide structural support during cell division – but it was not known that septins had anything to do with calcium signaling.

In the current study, the team discovered the septins formed a ring around the calcium channel and that without the septins’ involvement T cell activation does not occur.

—Findings appear in the journal Nature. News release at http://bit.ly/15lzeFp

Tiny RNA molecules pack a powerful punch

Scientists at The Scripps Research Institute (TSRI) have identified a family of tiny RNA molecules that work as powerful immune response regulators. The finding concerns a key interaction between T cells and B cells, the allied lymphocyte armies of the mammalian immune system. Antibody-producing B cells lie in wait for pathogens in special zones called follicles within lymph nodes and the spleen. But to start proliferating and pumping out fight-infection antibodies, B cells need an assist by “follicular helper” T cells (TFH cells) that migrate into the follicles and come into physical contact with the B cells.

In an effort to understand the molecular pathways of this process, researchers turned their attention to a family of RNA, known as miR-17~92s, believed to have a role in controlling TFH cell differentiation and migration.

Heretofore, researchers believed that suppression of miR-17~92 was required in controlling TFH cell differentiation and migration. To their surprise they found the opposite suggesting that instead of acting as a “brake” on TFH differentiation, miR-17~92s enables the process.

This was confirmed in mutant mice in which some or all of the miR-17~92 were knocked out of T cells. These miR-17~92-deficient T cells were less able to differentiate into TFH cells. In turn, the follicle-dwelling B cells that depend on TFH assistance also lost much of their ability to respond to an immune challenge.

Lynne Friedmann is a science writer based in Solana Beach.

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Posted by Staff on Jul 25, 2013. Filed under Columns, Editorial Columns, Research Report. You can follow any responses to this entry through the RSS 2.0. You can skip to the end and leave a response. Pinging is currently not allowed.

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