Immune response patterns in non-communicable inflammatory skin diseases

Abstract

Non-communicable inflammatory skin diseases (ncISD) such as psoriasis or atopic eczema are a major cause of global disease burden. Due to their impact and complexity, ncISD represent a major challenge of modern medicine. Dermatology textbooks describe more than 100 different ncISD based on clinical phenotype and histological architecture. In the last decades, this historical description was complemented by increasing molecular knowledge - and this knowledge is now being translated into specific therapeutics. Combining the enormous advances made in lymphocyte immunology and molecular genetics with clinical and histological phenotyping reveals six immune response patterns of the skin - type I immune cells cause the lichenoid pattern characterized by immune-mediated cell death of keratinocytes; type II immune cells underlie the eczematous pattern with impaired epidermal barrier, infection and eosinophils as well as the bullous pattern with loss of epithelial integrity; Th17 cells and ILC3 mediate the psoriatic pattern characterized by acanthosis, high metabolic activity and neutrophils; dysbalance of regulatory T cells causes either the fibrogenic pattern with rarefication of cells and dermal thickening or the granulomatous pattern defined by formation of granulomas. With more and more specific therapeutic agents approved, classifying ncISD also according to their immune response pattern will become highly relevant. This review defines the six immune response patterns of ncISD and highlights therapeutic strategies targeting key lymphocyte mediators.

Figure 1

Lymphocyte subsets drive distinct response patterns in the skin. Distinct lymphocyte subgroups differentiate out of common naïve precursor cells under specific micro‐environmental stimuli. Lymphocyte subsets are characterized by lineage‐defining transcription factors as well as secreted cytokines. These cytokines elicit six distinct cutaneous response patterns. Shown are representative histological and clinical pictures of each response pattern.

Figure 2

Efficacy of specific therapeutics in index diseases of each immune response pattern. Level of evidence is indicated by size, level of efficacy by colour of circles.

Figure 3

Immune response patterns in non‐communicable inflammatory skin diseases (ncISD). The pathogenesis of most ncISD is based on the interaction of lymphocytes and epithelial cells in the skin. Depending on the dominating lymphocyte subset, these interactions might be characterized by cytotoxic events (pattern I: lichenoid); reduced antimicrobial peptides, impaired skin barrier, and eosinophils (pattern II: eczematous); antibody deposits and blistering (pattern IIb: bullous); enhanced metabolism and neutrophils (pattern III: psoriatic); rarefication of cells and deposit of extracellular matrix (pattern IVa: fibrogenic); or granuloma formation (pattern IVb: granulomatous). [Correction added on 09 February after online publication: Figure 3 was missed out in previous version and has been added in this version].