Mast cells express IL-13αR1: IL-13 promotes human lung mast cell proliferation and FcεRI 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 alpha 1, is expressed on most leukocytes, except T-cells. Evidence to support IL-13R alpha 1 expression on mast cells is limited. Methods: We investigated: (i) IL-13R alpha 1 expression by human lung mast cells (HLMC); (ii) the number of IL-13R alpha 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 epsilon RI), stem cell factor receptor (CD117), histamine release, proliferation, and survival. Results: Human lung mast cell expressed IL-13R alpha 1 mRNA. IL-13R alpha 1 was highly expressed on the surface HLMC (82 +/- 9%). Bronchial submucosal mast cell IL-13R alpha 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 epsilon 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. Conclusions: Human lung mast cell express IL-13R alpha 1 and activation by IL-13 for 5 days increased Fc epsilon 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 epsilon RI expression. These data support the view that targeting IL-13 may be beneficial in the treatment of asthma.