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

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Background: The Th2 cytokine interleukin (IL)‐13 is implicated in the development of various allergic diseases including asthma. The IL‐13 receptor, IL‐13Rα1, is expressed on most leukocytes, except T‐cells. Evidence to support IL‐13Rα1 expression on mast cells is limited.Methods: We investigated: (i) IL‐13Rα1 expression by human lung mast cells (HLMC); (ii) the number of IL‐13Rα1+ 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 (FcɛRI), stem cell factor receptor (CD117), histamine release, proliferation, and survival.Results: Human lung mast cell expressed IL‐13Rα1 mRNA. IL‐13Rα1 was highly expressed on the surface HLMC (82 ± 9%). Bronchial submucosal mast cell IL‐13Rα1 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 FcɛRI 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‐13Rα1 and activation by IL‐13 for 5 days increased FcɛRI 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 FcɛRI expression. These data support the view that targeting IL‐13 may be beneficial in the treatment of asthma.