Targeting the Human βc Receptor Inhibits Contact Dermatitis in a Transgenic Mouse Model

Targeting the human βc receptor inhibits inflammatory myeloid cells and lung injury caused by acute cigarette smoke exposure

“…52 Here, we observed that CSL311 significantly reduced lung eosinophil numbers by about 40% in CS-exposed mice compared to isotype-treated mice, consistent with its effectiveness at reducing granulocytic infiltration and histopathology in a model of allergic contact dermatitis. 24 In addition to GM-CSF and IL-5, CSL311 inhibits signalling initiated by IL-3. Immune cells from hβ c Tg mice respond to mouse GM-CSF and IL-5 but not IL-3 under in vitro conditions, which may be due to instability of the complex formed between mIL-3, mIL3Rα and hβ c .…”

“…24 Under in vitro conditions, haematopoietic cells from hβ c Tg respond to mouse GM-CSF and IL-5 but not to IL-3, which indicates that the mouse IL-3Rα subunit does not efficiently interact with the human β c receptor subunit. 24 Mice were exposed to nine cigarettes per day period in an 18-L Perspex container that allows for free movement for four or 11 consecutive days, as previously described. 21,30 CSL311, a human monoclonal antibody that blocks β c cytokine signalling or matching isotype control antibody, 24,25 was administered via intravenous injection (50 mg/kg) on day 1, day 4, day 8 and day 11 prior to the CS exposure session.…”

“…24 Mice were exposed to nine cigarettes per day period in an 18-L Perspex container that allows for free movement for four or 11 consecutive days, as previously described. 21,30 CSL311, a human monoclonal antibody that blocks β c cytokine signalling or matching isotype control antibody, 24,25 was administered via intravenous injection (50 mg/kg) on day 1, day 4, day 8 and day 11 prior to the CS exposure session.…”

“…23 Inhibition of β c signalling in a model of allergic contact dermatitis also suppressed ear pinna thickening by reducing accumulation of neutrophils, mast cells and eosinophils in the skin. 24 To date, no study has tested the efficacy of a pan antagonist that targets the common cytokine-binding site within the human β c receptor in an acute CS exposure model. Here, we used our unique transgenic mouse model (human β c receptor transgenic [hβ c Tg] mice) expressing human β c 24 to show that when acutely exposed to CS, the anti-β c CSL311 antibody effectively blocks β c cytokine signalling with high potency.…”

“…24 To date, no study has tested the efficacy of a pan antagonist that targets the common cytokine-binding site within the human β c receptor in an acute CS exposure model. Here, we used our unique transgenic mouse model (human β c receptor transgenic [hβ c Tg] mice) expressing human β c 24 to show that when acutely exposed to CS, the anti-β c CSL311 antibody effectively blocks β c cytokine signalling with high potency. [25][26][27][28][29] We demonstrate that β c receptor signalling promotes infiltration of CD11b + macrophages including IMs and ExMs, neutrophils SUMMARY AT A GLANCE Myeloid cells, including macrophages, neutrophils and eosinophils, are important cellular drivers of inflammation and injury.…”