Plasmacytoid Dendritic Cells and Immunotherapy in Multiple Sclerosis

Felipe von Glehn; Leonilda M Santos; Konstantin E Balashov

Disclosures

Immunotherapy. 2012;4(10):1053-1061. 

In This Article

Involvement of pDCs in Human Diseases

Type I interferons are pleiotropic cytokines with antiviral activity that also enhance innate and adaptive immune responses.[24] However, chronic activation and secretion of type I interferons in the absence of infection can promote autoimmune diseases, for example, systemic lupus erythematosus (SLE) and psoriasis.[63] Furthermore, pDCs are able to migrate to affected peripheral tissues during inflammation, which lends further support to the view that pDCs are important players in innate and adaptive immunity in vivo.[40] For example, in psoriasis, early skin lesions are highly infiltrated with activated pDCs, corresponding with decreased numbers of circulating pDCs in the blood.[64] The aggregation of released cellular self-DNA and RNA into large complexes could efficiently activate pDCs,[29,65] although the origin of these immunostimulatory complexes remains to be elucidated. In SLE, the complexes of antinuclear antibodies and endogenous nucleic acid activate pDCs through TLR7 and TLR9, initiating type I interferon secretion.[66,67] SLE patients show increased serum levels of IFN-α/β that correlate with disease activity and severity.[68]

In rheumatoid arthritis, pDCs are recruited to the synovium where they may contribute to the local inflammatory environment. However, different from SLE and psoriasis, pDC concentration and phenotype in peripheral blood of patients with rheumatoid arthritis are similar to healthy subjects.[69,70]

BST-2 or tetherin, a ligand of ILT-7, is expressed in many tumors, suggesting a likely mechanism whereby these tumors prevent pDC activation and escape tumor surveillance.[20,71] HIV and hepatitis B virus may inhibit pDC function by binding to their surface molecule BDCA-2.[72,73]

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