Mast cells express IL‐13Rα1: IL‐13 promotes human lung mast cell proliferation and FcɛRI expression

Background: The Th2 cytokine interleukin (IL)‐13 is implicated in the development of various allergic diseases including asthma. The IL‐13 receptor, IL‐13R α 1, is expressed on most leukocytes, except T‐cells. Evidence to support IL‐13R α 1 expression on mast cells is limited. Methods: We investigated: (i) IL‐13R α 1 expression by human lung mast cells (HLMC); (ii) the number of IL‐13R α 1+ bronchial submucosal mast cells in subjects with asthma and normal controls and (iii) the effect of IL‐13 priming on HLMC expression of high‐affinity IgE receptor (Fc ɛ RI), stem cell factor receptor (CD117), histamine release, proliferation, and survival. Results: Human lung mast cell expressed IL‐13R α 1 mRNA. IL‐13R α 1 was highly expressed on the surface HLMC (82 ± 9%). Bronchial submucosal mast cell IL‐13R α 1 expression was higher in asthmatics (86 ± 2%) than normal controls (78 ± 2%; P = 0.015). IL‐13 priming for 30 min did not increase HLMC histamine release, in the presence or absence of SCF or in response to IgE/anti‐IgE activation. IL‐13 priming for 5 days upregulated HLMC Fc ɛ RI expression (22% increase in fluorescent intensity; P = 0.003), increased histamine release following IgE/anti‐IgE activation by 56% ( P = 0.03) and increased proliferation by 50% ( P = 0.003) without affecting cell survival or CD117 expression. The IL‐13 specific neutralizing antibody CAT‐354 inhibited all IL‐13 mediated effects. Conclusion: Human lung mast cell express IL‐13R α 1 and activation by IL‐13 for 5 days increased Fc ɛ RI expression and proliferation. Histamine release was not affected by short‐term priming with IL‐13, but was upregulated by priming for 5 days suggesting that this effect was mediated by the increased Fc ɛ RI expression. These data support the view that targeting IL‐13 may be beneficial in the treatment of asthma.