Discovery of new T-cell sub type opens window on Rheumatoid Arthritis

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Summary: Researchers have scrutinized the immune cells from patients with rheumatoid arthritis, revealing a striking new subset of T-cells that collaborate with other immune cells to drive inflammation in peripheral tissues.

A research team led by Scientists from Brigham and Women’s hospital (BWH) has scrutinized the immune cells from patients with rheumatoid arthritis, revealing a new subset of T-cells that collaborate with other immune cells to drive inflammation in peripheral tissues. The work that was propelled by technology enabled detailed analysis of even a handful of cells, opens critical window on the biology of the disease and suggests a strategy for the development of more precise and powerful treatments. They study is published in the online edition of the journal Nature.

The newest therapies for rheumatoid arthritis have helped transform our ability to treat the disease, they are fairly blunt instruments- blocking components of the immune system in a non-specific way.

Rheumatoid arthritis:

Is an auto immune condition where the immune system attacks the joints causing inflammation, pain and eventually destruction of tissues that make up this essential body part. The disorder affects roughly 1% of the world’s population and mostly women. Although there is significant evidence implicating T-cells- particularly their interactions with B-cells, which produce antibodies- it has been unclear which T-cell subtypes help orchestrate the damaging immune response that underlie RA.

Group of scientists set out to explore these questions by studying patient samples with remarkable detail. These were not possible in earlier studies. This disease deconstruction approach depends on sophisticated technologies, such as mass cytometry, that allowed researchers to rapidly shift through blood, joint tissue and the fluid surrounding joints to isolate specific cells defined by the assortment of molecules on their surfaces. They also harnessed RNA sequencing methods that can characterize even very small number of cells, revealing which genes are turned on and off.

With the help of these high-tech tools, researchers homed in on a unique population o f T-cells that are highly prevalent in the joints of RA patients. These cells, a kind of CD4+ or helper T cells represent roughly ¼ th of the helper T-cells found in patient’s joints.

These T cells do not adhere to conventional view of helper T cells is an interesting fact.

Researchers further analysed their unusual biological features. These T-cells are programmed to infiltrate parts of the body that are inflamed, and they stimulate B cells to produce antibodies. Antibodies are specialized proteins that usually recognize foreign substances and help rally the immune system to eliminate them.

In auto-immune diseases, these auto-antibodies instead recognize normal components of the human body and contribute to tissue damage. The Nature study represents the 1st detailed description of a type of T-cell with these features.

Researchers are seeking to understand the signals that coax these cells to develop and whether they play role in other autoimmune diseases such as Lupus, multiple sclerosis and type 1 diabetes. The team also plans to explore whether targeting these unique T-cells hold promise as a treatment for Rheumatoid arthritis.

This work is remarkable example of the power of our disease deconstruction approach. Researchers are hopeful that it will prove equally illuminating as we apply this to other immune-mediated diseases.