The contribution of IL-17 to the development of autoimmunity in psoriasis

Abstract

Psoriasis is an (auto)immune-mediated disease that manifests as widespread desquamative erythema. The TNF-α/IL-23/IL-17A axis is crucial to its pathogenesis, which is demonstrated by its excellent therapeutic response to biologics that target this axis. There is a strong association between HLA-C*0602 and psoriasis, and researchers have identified autoantigens that are restricted to this major histocompatibility class I molecule. These auto-Ags include LL-37, A disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5), and keratin 17. IL-17A-producing T cells have been identified in T cell populations that are reactive to these auto-Ags. In addition, lipid Ags have surfaced as candidate auto-Ags that activate IL-17A-producing T cells in a CD1a-restricted manner. In this article, we review the candidate auto-Ags that may contribute to the activation of the IL-17A-deviated immune response in psoriasis.

Keywords: A disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5; HLA-C*0602; LL-37; Psoriasis; autoimmunity; keratin 17.

Figure 1.

The simplified pathogenesis of psoriasis. Psoriasis is an (auto)immune-mediated inflammatory skin disease. Increased reactivity of T cells against autoantigens has been observed in psoriasis. Dendritic cells (DCs) present auto-Ags such as LL-37, ADAMTSL5, and keratin 17 in association with HLA-C*06:02. The phospholipase A2 group IV D (PLA2G4D) enzyme generates various lipid metabolites. Some lipid Ags are presented by DCs in association with CD1a. TNF-α and IL-23 produced by DCs induce IL-17A-producing T (T17) cells. IL-17A induces the proliferation of keratinocytes. IL-17A also induces the production of CXCL1, CXCL2, CXCL8, and IL-36 in keratinocytes, all of which stimulate neutrophil (Neu) migration into the epidermis. Moreover, IL-17A stimulates keratinocytes to produce CCL20, which recruits T17 cells. The TNF-α/IL-23/IL-17A axis plays a crucial role in the pathogenesis of psoriasis. ADAMTSL5; A disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5.