GARP reduces inflammation in a humanized mouse model of allergic airway disease

Soluble derivate of Glycoprotein A repetitions predominant (sGARP) has strong anti-inflammatory and regulatory properties in vitro as well as in vivo , represses proliferation and cytokine production of CD4 + T helper cells and induces CD4 + regulatory T cells (Treg). Furthermore, sGARP prevents inflammation in a preclinical in vivo humanized mouse model of graft versus host disease (Hahn SA et al. Blood 2013). Modulation of Treg function could have therapeutic effects in many inflammatory diseases. Hence, the aim of the present study was to investigate the impact of sGARP in treatment of allergic airway diseases by using an established humanized mouse model (Martin H et al. 2012). To address this question, adult NSG mice received peripheral blood mononuclear cells (PBMC) from birch pollen asthmatic patients. To analyze the effects of sGARP on allergic inflammation in the humanized mouse model, mice received additionally Treg alone or in combination with sGARP. The allergic airway disease was induced by a three-day intranasal challenge with birch pollen allergen 20 days after PBMC transfer. 48 hours after last challenge allergic inflammation was assessed by measurement of airway hyperresponsiveness (AHR), quantification of cells in the bronchoalveolar lavage (BAL) and analysis of human immune cells in different tissues by flow cytometric and histological staining. Additional transfer with sGARP significantly reduced AHR, total human immune cell counts, neutrophils and macrophages in the BAL, human CD4 + T and mucus producing goblet cells in the lungs. Hence, amplifying of Treg cell function via sGARP seems to be an effective treatment option for the suppression of allergic airway diseases.