I missed this last year! The answer to one of my long-lasting questions: is psoriasis a chronic inflammatory disease or an autoimmune disease?
For until today I thought it was a chronic inflammatory disease because, as yet, no autoantigen had been identified. Of course, this was puzzling as then it was difficult to understand what was triggering the disease so locally on the skin. How was it possible that nobody had found out the « allergic » culprit responsible for the reaction? I could not get this straight.
For instance Crohn disease is a chronic inflammatory disease, and we can blame the microbiota as the antigens triggering and maintaining the inflammation and the sustained T cell response. Could it be the same for psoriasis, the presence of a particular pathogen on the skin of the sensitive persons?
But there was also an other big difference between Crohn disease and psoriasis. People with Crohn disease did not seem at more risk for additional autoimmune diseases. And this contrasts to the fact that people with psoriasis are nearly twice as likely as people without psoriasis to develop additional autoimmune diseases. So how could we reconcile all this?
Today comes the answer I was looking for ! Thanks to the laboratory of Loredana Frasca who identified, for the first time, an autoantigen responsible for the activation of T cells. This was published in Nature Communication Lande et al 2015. They demonstrate that an antimicrobial peptide (called LL37), which is overexpressed in psoriatic skin, not only forms complexes with extracellular self-nucleic acids and chronically activates TLR7/8/9, but also directly stimulates T cells serving as an autoantigen presented by maturing DCs to T cells. Importantly, 46% of psoriasis patients and up to 75% in moderate-to-severe psoriasis patients have circulating LL37-specific T cells that produce pathogenic cytokines, including IL-17.
Now, how will this help to design new strategies to treat patient with psoriasis? May be since the LL37-specific T cells can be tracked in patient blood by tetramer staining, it is conceivable to imagine ways to specifically eliminate the autoimmune T cells and alleviate the symptoms and the disease. Long-term goal, then would probably aim to limit the production of LL-37 in the psoriasis lesion.
In any case, I am glad that 2016 (even if published in 2015) has already solved one of the mysteries I was not understanding!