Ficolin‐A Protects Against Allergic Asthma via Suppressing ILC2‐Drived Type 2 Inflammation

ABSTRACT Background Type 2 inflammation has emerged as a pivotal mechanism for asthma, which involves both innate and adaptive immunity. Human ficolin ( FCN )‐2 (L‐ficolin, P35 ) and its mouse homolog FCN ‐A are one of the major pattern recognition molecules of plasma/serum, acting as important initiators of the lectin complement system and playing important roles in immunity, including respiratory immunity. However, little is known about the role of FCN ‐2/A in allergic asthma. Methods Serum FCN ‐2 and IgE levels in 90 allergic asthmatic patients and 48 healthy controls were measured by ELISA . Aeroallergen house dust mite ( HDM )‐induced mouse model of asthma was generated in both wild type ( WT ) and FCN ‐A knockout ( KO ) mice. Mouse serum and bronchoalveolar lavage fluid ( BALF ) IgE levels, lung innate lymphoid cells ( ILC )1/2/3, the expression of transcription factors GATA3 , T‐bet, and RORγt , and the concentrations of type 2 cytokines in serum and BALF were measured by FCM , RT ‐ qPCR , Western blot, and ELISA . Results Serum FCN ‐2 concentrations in patients with allergic asthma were significantly lower than those in healthy controls. Similarly, lower serum and BALF FCN ‐A concentrations were observed in HDM ‐induced asthma mouse models compared to those of uninduced mice. In the asthma mouse model, FCN ‐A KO asthmatic mice had higher levels of total IgE and HDM ‐specific IgE ( sIgE ), β‐hexosaminidase (β‐ HEX ) and histamine secretion, as well as increased airway epithelial permeability with the release of FITC ‐dextran in sera, inflammatory cell infiltration and eosinophil counts, and displayed more severe disease symptoms with histological damage compared to WT asthmatic mice. FCN ‐A KO asthmatic mice showed decreased T‐bet + ILC1 and increased IL ‐5 + / IL ‐13 + ILC2 / ILC2 proportions, p‐ GATA3 expression, serum and BALF type 2 cytokines IL ‐4, IL ‐5, and IL ‐13, Th17 cytokine IL ‐17, and chemokines CCL2 /4 production. Importantly, the administration of exogenous FCN ‐A protected against mouse allergic airway inflammation with decreased ILC2 proportions and type 2 cytokines expression, serum total and allergen‐specific IgE production. These results suggest that FCN ‐A suppresses both ILC2 innate immunity and IgE ‐mediated adaptive immunity during asthma. Conclusion Our findings provide previously unreported evidence that FCN ‐A protects against allergic asthma by suppressing lung ILC2 ‐driven type 2 inflammation.