Allergic inflammation triggers dyslipidemia via IgG signalling

Author:

Fernández‐Gallego Nieves12ORCID,Castillo‐González Raquel13ORCID,Moreno‐Serna Lucía2ORCID,García‐Cívico Antonio J.45ORCID,Sánchez‐Martínez Elisa2ORCID,López‐Sanz Celia2ORCID,Fontes Ana Luiza6ORCID,Pimentel Lígia L.6ORCID,Gradillas Ana5ORCID,Obeso David45ORCID,Neuhaus René45,Ramírez‐Huesca Marta1,Ruiz‐Fernández Ignacio1ORCID,Nuñez‐Borque Emilio7ORCID,Carrasco Yolanda R.8ORCID,Ibáñez Borja1910ORCID,Martín Pilar110ORCID,Blanco Carlos11,Barbas Coral5ORCID,Barber Domingo4ORCID,Rodríguez‐Alcalá Luis M.6ORCID,Villaseñor Alma45ORCID,Esteban Vanesa712ORCID,Sánchez‐Madrid Francisco1210ORCID,Jiménez‐Saiz Rodrigo281314ORCID

Affiliation:

1. Centro Nacional de Investigaciones Cardiovasculares (CNIC) Madrid Spain

2. Department of Immunology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐Princesa) Universidad Autónoma de Madrid (UAM) Madrid Spain

3. Department of Immunology, Ophthalmology and Ear, Nose and Throat (ENT) Universidad Complutense de Madrid Madrid Spain

4. Department of Basic Medical Sciences, Faculty of Medicine, Instituto de Medicina Molecular Aplicada (IMMA) Universidad San Pablo‐CEU, CEU Universities Madrid Spain

5. Centro de Metabolómica y Bioanálisis (CEMBIO), Faculty of Pharmacy, Universidad San Pablo‐CEU CEU Universities Madrid Spain

6. CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia Universidade Católica Portuguesa Porto Portugal

7. Department of Allergy and Immunology, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS‐FJD) Universidad Autónoma de Madrid (UAM) Madrid Spain

8. Department of Immunology and Oncology Centro Nacional de Biotecnología (CNB)‐CSIC Madrid Spain

9. Department of Cardiology Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS‐FJD) Madrid Spain

10. CIBER de Enfermedades Cardiovasculares (CIBERCV) Instituto de Salud Carlos III Madrid Spain

11. Department of Allergy Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐Princesa) Madrid Spain

12. Faculty of Medicine and Biomedicine Universidad Alfonso X El Sabio Madrid Spain

13. Department of Medicine, McMaster Immunology Research Centre (MIRC), Schroeder Allergy and Immunology Research Institute (SAIRI) McMaster University Hamilton Ontario Canada

14. Faculty of Experimental Sciences Universidad Francisco de Vitoria (UFV) Madrid Spain

Abstract

AbstractBackgroundAllergic diseases begin early in life and are often chronic, thus creating an inflammatory environment that may precede or exacerbate other pathologies. In this regard, allergy has been associated to metabolic disorders and with a higher risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood.MethodsWe used a murine model of allergy and atherosclerosis, different diets and sensitization methods, and cell‐depleting strategies to ascertain the contribution of acute and late phase inflammation to dyslipidemia. Untargeted lipidomic analyses were applied to define the lipid fingerprint of allergic inflammation at different phases of allergic pathology. Expression of genes related to lipid metabolism was assessed in liver and adipose tissue at different times post‐allergen challenge. Also, changes in serum triglycerides (TGs) were evaluated in a group of 59 patients ≥14 days after the onset of an allergic reaction.ResultsWe found that allergic inflammation induces a unique lipid signature that is characterized by increased serum TGs and changes in the expression of genes related to lipid metabolism in liver and adipose tissue. Alterations in blood TGs following an allergic reaction are independent of T‐cell‐driven late phase inflammation. On the contrary, the IgG‐mediated alternative pathway of anaphylaxis is sufficient to induce a TG increase and a unique lipid profile. Lastly, we demonstrated an increase in serum TGs in 59 patients after undergoing an allergic reaction.ConclusionOverall, this study reveals that IgG‐mediated allergic inflammation regulates lipid metabolism.

Funder

Instituto de Salud Carlos III

Ministerio de Ciencia e Innovación

Ministerio de Universidades

Comunidad de Madrid

Publisher

Wiley

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