The Role of Plasmacytoid Dendritic Cells and Interferon-Alpha in the Immunopathogenesis of Psoriasis

Sir,

I read with great interest the recent review by Coondoo,[1] and specifically on the topic immunopathogenesis of psoriasis, I have the following comments to offer:

In addition to overexpression of several pro-inflammatory cytokines such as interleukin-2 (IL-2), IL-6, IL-8, IL-12, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) by Th1 cells described by the author,[1] interferon-alpha (IFN-α) produced by activated plasmocytoid dendritic cells (pDCs) has been found to contribute to the pathophysiology of psoriasis.[2–6]

High amounts of IFN-α produced by activated pDCs induce a strong activation of the local immune system (mainly myeloid dendritic cells and potentially autoreactive T cells) that become capable of secreting cytokines that further promote an pathogenic inflammatory cascade.[7] For this to occur, pDCs infiltrate the dermis of psoriasis patients and become active to produce IFN-α early during disease development.[2] The earliest event seems to be the conversion of pro-chemerin into chemerin in psoriatic pre-lesionnal skin leading to the recruitment of ChemR23 expressing pDCs and the antimicrobial peptide LL37 (also known as CAMP) has been identified as the key factor that mediates pDCs activation in psoriasis lesions.[3,4] Recently, also was demonstrated that the histamine H4 receptor is highly expressed on pDCs in psoriasis and histamine influences cytokine production and migration of pDCs.[5] Other report[6] showed that sun exposure rapidly reduces pDCs in psoriatic lesional dermis preceded clinical improvement. These findings suggest that suninduced clinical benefit may partly be explained by its effect on pDCs and their products.[6]

Moreover, there are other interesting studies that support such close relationship between IFN-α and the onset of psoriatic lesions.[8–11] There are cases of psoriasis development or exacerbation after injection of recombinant IFN-α or the topical application of imiquimod (a potent IFN-α inducer).[8,9] Psoriatic lesions induced by anti-TNF-α (pharmacological class with remarkable efficacy in the treatment of the psoriasis) have also been described worldwide.[10,11] Since pDCs are normally downregulated by TNF-α through the inhibition of the maturation of their hematopoietic precursors, TNF-α inhibition by the biological may determine increased and uncontrolled IFN-α production and generate, as a result, the onset and/or aggravation of psoriasis.[10,11] A study[10] detected strong production of protein MxA (represents a specific marker for IFN signaling) in the inflammatory cells of skin samples of anti-TNF-α-induced psoriasis. Another report[11] found increased IFN-α expression in the psoriatic lesions of patients under anti-TNF-α therapy.

Finally, these findings[2–6] suggest that both pDCs and IFN-α may be potential early therapeutic targets in psoriasis treatment.