Key first steps to inflammatory arthritis identified

Neutrophils within the joint also produce chemokines that amplify the cells' recruitment and survival in joint spaces.

Published: 23rd January 2017 01:55 PM  |   Last Updated: 23rd January 2017 01:55 PM   |  A+A-

Arthritis

By PTI

BOSTON: In an advance that may lead to new therapies to treat inflammatory arthritis, scientists have identified the initial steps leading to joint inflammation using a novel approach for imaging movement of immune cells in living animals.

Researchers found that expression of a specific molecule - complement C5a - is required to cause the immune cells called neutrophils to adhere to joint surfaces and migrate into the joint, a process known to set off the inflammatory cascade. "Inflammatory arthritis is caused when immune cells are recruited from the blood into the joint in a highly regulated process controlled by chemoattractants and adhesion receptors," said Andrew Luster from the Massachusetts General Hospital (MGH) in the US.

"But when the disease has become symptomatic, it is difficult to determine the initial steps that set off the recruitment of immune cells into the joint and the specific roles of the different chemoattractants," Luster said. Inflammatory arthritis includes a number of autoimmune diseases of the joints - including rheumatoid arthritis and lupus - and in many cases is caused by a type of inflammation called type III hypersensitivity. That reaction results when a localised accumulation of immune complexes - antibodies bound to their antigens - is deposited in tissue and sets off an inflammatory response involving the infiltration and activation of immune cells, initially the neutrophil.

Current thinking regarding type III hypersensitivity is that immune cells within tissues sense the presence of these immune complexes (ICs) through specific receptor molecules and release inflammatory factors called cytokines that activate the endothelial cells lining adjacent blood vessels to promote the recruitment of neutrophils. Researchers used multiphoton intravital microscopy - an imaging technology for studying immune cell movements in living animals - to follow in real time the development of IC-induced arthritis in a mouse model of rheumatoid arthritis.

The experiments showed that the presence of ICs within the joint space induces the generation of complement C5a, a component of the innate immune system, which is then displayed on the inner walls of adjacent blood vessels. C5a initiates the adherence of neutrophils to vessel walls through interaction with the C5a receptor on neutrophils, which then pass into the joint space and set off inflammation. Once the inflammatory process is initiated, neutrophils in the joint space release interleukin-1, which induces cells to produce chemoattractants or chemokines that facilitate the further movement of neutrophils into the joint space.

Neutrophils within the joint also produce chemokines that amplify the cells' recruitment and survival in joint spaces. "The control of immune cell entry into joints represents a major point at which new therapies could be developed to reduce the symptoms of inflammatory arthritis," said Luster. The study appears in the journal Science Immunology.

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