Human IL22 blocking peptide

Objective: The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) within genes involved in inflammation, skin barrier integrity, signaling/pattern recognition, and antioxidant defense with irritant susceptibility in a group of health care workers. Methods: The 536 volunteer subjects were genotyped for selected SNPs and patch tested with three model irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH), and benzalkonium chloride (BKC). Genotyping was performed on genomic DNA using Illumina Goldengate custom panels. Results: The ACACB (rs2268387, rs16934132, rs2284685), NTRK2 (rs10868231), NTRK3 (rs1347424), IL22 (rs1179251), PLAU (rs2227564), EGFR (rs6593202), and FGF2 (rs308439) SNPs showed an association with skin response to tested irritants in different genetic models (all at P < 0.001). Functional annotations identified two SNPs in PLAU (rs2227564) and ACACB (rs2284685) genes with a potential impact on gene regulation. In addition, EGF (rs10029654), EGFR (rs12718939), CXCL12 (rs197452), and VCAM1 (rs3917018) genes showed an association with hand dermatitis (P < 0.005). Conclusions: The results demonstrate that genetic variations in genes related to inflammation and skin homeostasis can influence responses to irritants and may explain inter-individual variation in the development of subsequent contact dermatitis.

Severe bacterial (pneumococcal) infections are commonly associated with influenza and are significant contributors to the excess morbidity and mortality of influenza. Disruption of lung tissue integrity during influenza participates in bacterial pulmonary colonization and dissemination out of the lungs. Interleukin-22 (IL22) has gained considerable interest in anti-inflammatory and anti-infection immunotherapy over the last decade. In the current study, we investigated the effect of exogenous IL-22 delivery on the outcome of pneumococcal superinfection postinfluenza. Our data show that exogenous treatment of influenza virus-infected mice with recombinant IL-22 reduces bacterial dissemination out of the lungs but is without effect on pulmonary bacterial burden. Reduced systemic bacterial dissemination was linked to reinforced pulmonary barrier functions, as revealed by total protein measurement in the bronchoalveolar fluids, intratracheal fluorescein isothiocyanatedextran tracking, and histological approaches. We describe an IL-22-specific gene signature in the lung tissue of influenza A virus (IAV)-infected (and naive) mice that might explain the observed effects. Indeed, exogenous IL-22 modulates the gene expression profile in a way that suggests reinforcement of tissue integrity. Our results open the way to alternative approaches for limiting postinfluenza bacterial superinfection, particularly, systemic bacterial invasion.