![]() In the absence of foreign antigens, clonal T cell expansion is highly suggestive for autoimmunity in inflammatory diseases ( 34). Activation and clonal expansion of T cells occur upon antigenic stimulation. In general, both HLA restriction and peptide specificity of a given T cell are determined by its T cell receptor (TCR) repertoire ( 33). Finally, the more recent discoveries that complexes of the antimicrobial peptide L元7 (a 37 amino acid C-terminal cleavage product of the antimicrobial peptide, cathelicidin) with own DNA or the melanocytic antigen ADAMTSL5 may function as autoantigens ( 27, 28), support the central role of T cells in the pathogenesis of psoriasis ( 29, 30). In addition, psoriasis-like skin inflammation in animal models can be initiated by certain CD4+ T cells ( 21– 24), and T cells can induce psoriatic lesions in human skin xenografts ( 25, 26). IL-10 can also ameliorate psoriatic symptoms by modulating T cell functions ( 20). A therapeutic effect can also be achieved by interleukin (IL)-4, which pushes the cytokine milieu toward a T-helper (Th) cell 2-dominated immune response ( 16), probably through attenuation of Th17 function following diminished IL-23 production in antigen-presenting cells ( 17) and through induction of the transcription factor GATA3 ( 18, 19). Drugs that specifically inhibit the function of T lymphocytes (such as CD2 blockade in the early days of biologics) can improve psoriasis ( 15). This view is substantiated by numerous subsequent observations over the past four decades: psoriasis can be precipitated by bone marrow transplantation ( 11) and, similar to other autoinflammatory diseases, the disease is frequently associated with certain HLA expression patterns ( 7, 12– 14). ![]() Since it was shown in the late 1970s that psoriasis can be ameliorated by cyclosporin A ( 10), it can no longer be seriously denied that T lymphocytes play a central role in the pathogenesis of this disease. The disease is based on close interactions between components of the adaptive and the innate branches of the immune system ( 3, 5– 9) ( Figure 1). Research into its pathophysiology has led to impressive therapeutic improvements ( 3, 4). Psoriasis is currently viewed as a systemic chronic inflammatory disease with an immunogenetic basis that can be triggered extrinsically or intrinsically ( 1, 2). If I was to name diseases that in recent years have increased our understanding of both adaptive and innate immune mechanisms on the one hand and have contributed decisively to the development of modern biological therapies on the other, then psoriasis would certainly occupy one of the top ranks. Setting the Stage: Psoriasis as an Immune-Mediated Disorder This review sets into context the current knowledge about innate and adaptive immunological processes in psoriasis and other autoimmune or autoinflammatory diseases. While such associations have been suspected for many years, compelling mechanistic evidence in support of this notion is still scant. ![]() Specific adaptive autoimmune responses, together with our current view of psoriasis as a systemic inflammatory disorder, raise the question of whether psoriasis may have connections to autoimmune or autoinflammatory disorders elsewhere in the body. These findings are accompanied by various immunoregulatory mechanisms, which we increasingly understand and which connect innate and adaptive immunity. Indeed, some studies suggested antigenic functions of structural proteins, and complexes of self-DNA with cathelicidin (L元7) or melanocytic ADAMTSL5 have been proposed more recently as actual auto-antigens in some cases of psoriasis. There is accumulating clinical and experimental evidence suggesting that both autoimmune and autoinflammatory mechanisms lie at the core of the disease. This includes the association of psoriasis with certain MHC (HLA) alleles, oligoclonal expansion of T cells in some cases, therapeutic response to T cell-directed immunomodulation, the onset of psoriasis following bone marrow transplantation, or induction of psoriasis-like inflammation by T cells in experimental animals. Over the past three decades, a considerable body of evidence has highlighted T cells as pivotal culprits in the pathogenesis of psoriasis. Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany. ![]()
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