• Transl Res · Oct 2024

    PCSK9 inhibition protects mice from food allergy.

    • Victoria Lorant, Martin Klein, Damien Garçon, Thibaud Sotin, Samuel Frey, Marie-Aude Cheminant, Audrey Ayer, Mikaël Croyal, Laurent Flet, Antoine Rimbert, Luc Colas, Bertrand Cariou, Grégory Bouchaud, and Le MayCédricCNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, 8 quai Moncousu, BP70721, Nantes 44000, France. Electronic address: cedric.lemay@univ-nantes.fr..
    • Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, 8 quai Moncousu, BP70721, Nantes 44000, France.
    • Transl Res. 2024 Oct 1; 272: 151161151-161.

    AbstractThe Proprotein Convertase Subtilisin Kexin of type 9 (PCSK9) has been identified in 2003 as the third gene involved in familial hypercholesterolemia. PCSK9 binds to the membrane low-density lipoprotein receptor (LDLR) and promotes its cellular internalization and lysosomal degradation. Beyond this canonical role, PCSK9 was recently described to be involved in several immune responses. However, to date, the contribution of PCSK9 in food allergy remains unknown. Here, we showed that Pcsk9 deficiency or pharmacological inhibition of circulating PCSK9 with a specific monoclonal antibody (m-Ab) protected mice against symptoms of gliadin-induced-food allergy, such as increased intestinal transit time and ear oedema. Furthermore, specific PCSK9 inhibition during the elicitation steps of allergic process was sufficient to ensure anti-allergic effects in mice. Interestingly, the protective effect of PCSK9 inhibition against food allergy symptoms was independent of the LDLR as PCSK9 inhibitors remained effective in Ldlr deficient mice. In vitro, we showed that recombinant gain of function PCSK9 (PCSK9 D374Y) increased the percentage of mature bone marrow derived dendritic cells (BMDCs), promoted naïve T cell proliferation and potentiated the gliadin induced basophils degranulation. Altogether, our data demonstrate that PCSK9 inhibition is protective against gliadin induced food allergy in a LDLR-independent manner.Copyright © 2024. Published by Elsevier Inc.

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