Increased circulating Th17 frequencies and serum IL‐22 levels in patients with acute generalized exanthematous pustulosis

Abstract

Th17 cells and their produced cytokine IL-22 were elevated in the peripheral blood of patients with AGEP. As IL-17 and IL-22 cooperatively stimulate keratinocytes to produce IL-8, IL-8 may contribute to the accumulation of neutrophils in the lesional epidermis of AGEP.

Acute Generalized Exanthematous Pustulosis: Pathogenesis, Genetic Background, Clinical Variants and Therapy

“…Recently, it has also been shown that, besides in toxic epidermal necrolysis (TEN), granulysin is also expressed by CD4 and CD8 T cells and natural killer (NK) cells in different drug reactions including AGEP, suggesting that granulysin may also play a role in the pathogenesis of AGEP [28]. Furthermore, in vitro tests have shown that drug-specific T cells in AGEP patients produced significantly more chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, a potent neutrophil chemotactic chemokine [26,27,28,29]. CXCL8/IL-8 is thought to play a central role in the formation of pustules by recruitment of neutrophils.…”

Pyoderma gangrenosum: challenges and solutions

“…[8][9][10] The similarities between PG and neutrophilic diseases suggest that underlying common inflammatory pathways probably converge to their pathophysiology, leading to abnormalities in polymorphonuclear neutrophils (PMN) recruitment or homeostasis. 8 In PG and other neutrophilic diseases, elevated skin and/or circulating levels of the pro-inflammatory cytokines (IL1β, IL6, TNF-α, IFN-ϒ, G-CSF) [10][11][12] and, particularly, of the potent PMN attracting chemokines, namely IL8/CXCL8 and CXCL1,2,3, along with skin infiltration by T cells, particularly at the edge of the PG ulcer, suggests an active recruitment of PMN to the skin. 10,13 Also, in both PG and SS skin lesions, there is a high expression of MMPs (MMP-2, MMP-9, MMP-10), a family of Zn2+ endopeptidades that are not only major contributors to the breakdown and reconstitution of the extracellular matrix in wound repair, but also influence the production of neutrophilic chemokines in neutrophilic disorders.…”

“…10,13,14 IL17 produced by Th17 cells, shown to play an important role in IBD and other skin diseases that involve neutrophil recruitment, like psoriasis and acute generalized exanthematous pustulosis, has also been found to be elevated in skin lesions of PG. 12,[14][15][16] Th17 cells seem to be overrepresented in PG lesions together with a low level of regulatory T cells (Treg) and related cytokines, namely IL10. 17 However, in a more recent case, IL17 was not significantly elevated in PG, whereas IL23, responsible for driving T cells into the Th17 phenotype, was elevated and was considered the support for therapy with ustekinumab, a monoclonal antibody that binds the shared p40 subunit of IL23 and IL12.…”

Paediatric Acute Generalized Exanthematous Pustulosis Induced by Paracetamol with High Serum Levels of Interleukin-8 and -22: A Case Report

“…IL-17 and IL-22 exert a strong synergistic effect on the production of IL-8 by keratinocytes (14). Increased frequencies of Thl7 cells and high levels of IL-22 have been reported in AGEP (15,16).…”