Anti-IL19 polyclonal antibody

Author summary The immune response toSarcoptes scabieiinfestation is poorly defined. There have been few studies of crusted scabies, a debilitating clinical variant of the disease characterised by extremely high mite numbers. In this study, we used a pig model to explore differences in gene expression between clinical variants of scabies, including a focus on immune events occurring prior to the development of clinical signs. In early infestation, genes relating to inflammation, immune recognition and cell migration were potently suppressed in pigs with crusted scabies. This suggests that these pigs lacked the ability to mount a timely, effective immune response, allowing mites to proliferate unchecked. In later infestation, the large numbers of mites then triggered a strong inflammatory response leading to severe skin pathology. Gene expression profiles in crusted scabies shared similarities with other inflammatory skin diseases such as psoriasis. This is the first study to compare immune responses in crusted and ordinary scabies in early infestation and reveals new insights into the progression of disease. Findings may lead to the development of new approaches to diagnose and treat this important, but neglected disease. Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation ofSarcoptes scabieimites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating disease.

Asthma is a chronic inflammatory disease of the airway. Its major symptoms are reversible breathing problems causing airway narrowing and obstruction. IL-19 is a member of the IL-10 family cytokines. We previously showed that IL-19 induces T-helper 2 (Th2) cytokines and that asthma patients had higher serum IL-19 levels. To further examine whether inhibiting IL-19 and its receptor (IL-20R1) protected rodents against asthma, we used Dermatophagoides pteronyssinus (Der p; house dust mites) to induce chronic airway inflammation in wild-type C57BU6 and IL-20R1-deficient mice and then analyzed the effect of the IL-20R1 deficiency on the pathogenesis of asthma. We also examined whether inhibiting IL-19 and IL-20R1 ameliorated Der p-induced chronic asthma. Der p induced IL-19 in lung airway epithelial cells, type 2 alveolar cells, and alveolar macrophages. An IL-20R1 deficiency abolished IL-19-induced Th2 cell differentiation in vitro. Th2 cytokine expression, immune cell infiltration in the bronchoalveolar lavage, airway hyperresponsiveness (AHR), and bronchial wall thickening were lower in Der p-challenged IL-20R1-deficient mice. Anti-IL-20R1 monoclonal antibody (mAb) 51D and IL-19 polyclonal antibody (pAb) both ameliorated Der p-induced AHR, lung immune cell infiltration, bronchial wall thickening, and Th2 cytokine expression. Moreover, we confirmed that anti-IL-19 mAb (1BB1) attenuated lung inflammation in a rat ovalbumin-induced asthma model. This is the first report to show that inhibition of IL19 by targeting IL-19 or IL-20R1 protected rodents from allergic lung inflammation. Our study suggests that targeting IL-19 signaling might be a novel therapeutic strategy for treating allergic asthma.