Interleukin‐21 in autoimmune and inflammatory skin diseases

Abstract

Studies on the role of interleukins (ILs) in autoimmune and inflammatory diseases allow for the better understanding of pathologic mechanisms of disease and reshaping of treatment modalities. The development of monoclonal antibodies targeting specific ILs or IL signaling pathways (i.e., anti‐IL‐17/IL‐23 in psoriasis or anti‐IL‐4/IL‐13 in atopic dermatitis) is the shining example of therapeutic interventions in research. IL‐21, belonging to the group of ɣc‐cytokines (IL‐2, IL‐4, IL‐7, IL‐9, and IL‐15), is gaining attention for its pleiotropic role in several types of immune cells as activator of various inflammatory pathways. In both health and disease, IL‐21 sustains T‐ and B‐cell activity. Together with IL‐6, IL‐21 helps to generate Th17 cells, promotes CXCR5 expression in T cells, and their maturation into follicular T helper cells. In B cells, IL‐21 sustains their proliferation and maturation into plasma cells and promotes class switching and antigen‐specific antibody production. Due to these characteristics, IL‐21 is a main factor in numerous immunologic disorders, such as rheumatoid arthritis and MS. Studies in preclinical skin disease models and on human skin strongly suggest that IL‐21 is crucially involved in inflammatory and autoimmune cutaneous disorders. Here, we summarize the current knowledge of IL‐21 in well‐known skin diseases.

Cut-off values for IL-21 and IL-23 as biochemical markers for pemphigus vulgaris

“…Furthermore, resident memory T cells similar to Tfh mainly express IL-17 and IL-21. These results suggest that T-dependent immune responses and IL-21 are involved in pemphigus [ 34 ].…”

Pemphigus and pemphigoids: Clinical presentation, diagnosis and therapy

“…Pathogenically, the crucial event in pemphigus is the formation of antibodies binding desmosomal proteins, leading to a loss of keratinocyte adhesion 23 . Formation of autoantibodies is supported by autoreactive, human leukocyte antigen (HLA)‐restricted T‐cells, which demonstrate a prevalently Th2 but also Th17‐oriented phenotype during active disease 24–26 . HLA DRB1*04: 02 and HLA‐DQB1*05: 03 increase risk of pemphigus.…”

“…23 Formation of autoantibodies is supported by autoreactive, human leukocyte antigen (HLA)-restricted T-cells, which demonstrate a prevalently Th2 but also Th17-oriented phenotype during active disease. [24][25][26] HLA DRB1*04: 02 and HLA-DQB1*05: 03 increase risk of pemphigus. Concordantly, these HLA types are more prevalent in geographical regions where pemphigus is more frequent.…”

Pemphigus‐ und Pemphigoid‐Erkrankungen: Klinik, Diagnostik und Therapie

“…Pathogenetisch führt die Bindung von Antikörper an desmosomale Proteine zu einem Verlust der Keratinozytenadhäsion 23 . Die Bildung von Autoantikörpern wird durch autoreaktive, auf humane Leukozytenantigene (HLA) beschränkte T‐Zellen unterstützt, die während der aktiven Erkrankung einen überwiegend Th2‐, aber auch Th17‐orientierten Phänotyp aufweisen 24–26 . HLA DRB1*04: 02 und HLA‐DQB1*05:03 erhöhen das Risiko für Pemphigus.…”

“…23 Die Bildung von Autoantikörpern wird durch autoreaktive, auf humane Leukozytenantigene (HLA) beschränkte T-Zellen unterstützt, die während der aktiven Erkrankung einen überwiegend Th2-, aber auch Th17-orientierten Phänotyp aufweisen. [24][25][26] Pemphigus vulgaris (PV) ist durch zirkulierende IgG-Autoantikörper gegen Dsg3 und Dsg1 gekennzeichnet, die Akantholyse und suprabasale Blasenbildung an Haut und Schleimhäuten verursachen. 38 Das klinische Bild korreliert mit dem Antikörperprofil.…”