Stopping of a type of regulated cell death called necroptosis in keratinocytes is critical for the prevention of skin inflammation, according to new research from Germany.
International report - Stopping of a type of regulated cell death called necroptosis in keratinocytes is critical for the prevention of skin inflammation, according to new research from Germany.
A University of Cologne study has identified a surprising new mechanism of inflammatory skin lesions - a deficiency in the Fas-associated death domain (FAAD) adaptor protein. The work in the mouse model was published in the journal Immunity.
The FAAD protein is important for the regulation of necroptosis in keratinocytes and thus the maintenance of immune homeostasis and the prevention of chronic inflammation.
"Apoptosis is cell death induced by activation of caspases; necroptosis is cell death usually induced in cells where the caspases are inactive. The two different types ... are distinct morphologically and also molecularly in their different signaling pathways," he says.
Dr. Pasparakis says the discovery began by accident. Researchers were developing a new strain of genetic knockout mice to study inflammation and apoptosis and observed spontaneous necrosis of keratinocytes and development of severe inflammatory skin lesions in the animals within the first few days of birth.
Investigators were surprised by the unanticipated results and repeated the experiment, only to see the same outcome. "We never expected that these mice would develop a phenotype of their own," Dr. Pasparakis says. "It took us more than four years of work to clarify the mechanism."