JAML – activator of epithelial immunity
Scientists have found the key to wound healingABC magazine based on EurekAlert! – Scientists discover the mechanisms and function of a type of mysterious immune cell.
Two groups of scientists from the Scripps Research Institute have published a joint report on the results of two parallel studies of gamma/delta T lymphocytes - immune cells mainly found in epithelial tissues.
"These cells play a key role in damage or diseases affecting the epithelium," explains the head of one of the studies, Professor Wendy Havran of the Scripps Institute. Havran's group was able to detect a molecule involved in the regulation of the behavior of gamma/delta T-lymphocytes in epithelial tissue damage. The second group, led by Ian Wilson, focused on studying the mechanisms of this subgroup of immune cells, which had previously remained unknown.
For 30 years since the discovery of gamma/delta T-lymphocytes, scientists have found out that they are formed in the thymus at the stage of embryonic development, after which they migrate to epithelial tissues. Unlike alpha/beta T-lymphocytes, which make up 90% of immune cells and perform the "find and destroy" function, most gamma/delta T-lymphocytes do not enter the blood. They are the main immune component of the skin, lungs and intestines, where they protect the epithelium from damage and infections.
Havran's team has unraveled the mechanism by which gamma/delta T lymphocytes accelerate the healing processes of damaged epithelium. It turned out that keratinocytes, when cells are damaged, begin to synthesize a signaling protein that is recognized by gamma/delta T lymphocytes. This triggers the process of morphological changes of the immune cells themselves and their transition to the mode of mass production of growth factors that bind to keratinocytes and other epithelial cells, accelerating their reproduction and, thus, leading to the elimination of tissue damage. The gamma/delta T-lymphocytes themselves also divide intensively, which further accelerates the process.
Scientists have managed to isolate a molecule that is a co-stimulator for the activation of gamma/delta T-lymphocytes – a connective adhesive molecule JAML (junctional adhesion molecule), which, by binding to the CAR receptors (coxsackie and adenovirus receptor) of damaged keratinocytes, triggers the process of complete activation of gamma/delta T-lymphocytes.
Using the method of X-ray crystallography, scientists were able to observe the process of JAML-CAR interaction at the molecular level. Later, it was possible to obtain physiological confirmation of the scientists' correctness in experiments on laboratory mice: blocking JAML-CAR interaction led to a violation of the activation of gamma/delta T-lymphocytes and subsequent healing processes of epithelial tissue damage.
Scientists believe that the data they have obtained are relevant for patients with a number of chronic diseases that lead to epithelial damage, including diabetes, extensive burns, bedsores. And the detection of a molecule that activates gamma/delta T lymphocytes gives pharmacists a potential target for controlling the healing processes of damaged epithelium.
Portal "Eternal youth" http://vechnayamolodost.ru06.09.2010