LL37 identified as an auto antigen in Psoriasis

According a new study published in nature communications, anti-microbial peptide (AMP) LL37 acts as an auto antigen in psoriasis. The study shows that LL37 was recognized as an antigen by circulating T cells in 46% of psoriatic patients. This recognition was shown by proliferation of T cells and production of interferon gamma in response to LL37. None of the controls showed such response.

Roberto Lande and colleagues from Italy and Switzerland published their findings in December issue of Nature communications. They performed their research using blood from psoriasis patients.

Psoriasis is a common condition of skin characterized by development of red scaly plaques on skin. Although it is sometimes considered an autoimmune disease, the nature of the auto antigen that leads to development of auto reactive T cells is not known. LL37 is an AMP that has been shown to be overexpressed in psoriatic skin and play important roles in pathogenesis of psoriasis. It forms complexes with extracellular self-nucleic acid. These complexes then activate plasmatoid and myeloid DCs which in turn leads to activation of T helper cells. This process then starts an inflammatory cascade. However, it was not known if LL37 can directly serve as an auto-antigen and stimulate T cells.

In this study, the authors established that psoriatic T cells were specifically responding to LL37 by showing that T cells respond only to LL37 when stimulated with a variety of other AMPs. The authors also looked at correlation of response to LL37 and disease status and found that up to 75% of psoriatic patients with moderate to severe plaque psoriasis and with a Psoriasis Activity Severity Index (PASI) score of more than 10 responded to LL37. The LL37 specific T cells in psoriasis patients showed production of pathogenic cytokines including IL17 as well as showed direct chemo tactic activity for inflammatory cells and cytotoxic ability. The study also showed that these T cells possess the ability to migrate into psoriatic skin lesions. This was further validated by finding of LL37 specific cell from skin biopsy of a psoriatic patient who earlier showed positive response of blood T cells to LL37.

In conclusion, this study shows that LL37 is an auto antigen in psoriasis and could be an appealing target to treat psoriasis.