Atherosclerosis is responsible for a large percentage of all-cause mortality worldwide, but it is only now beginning to be understood as a complex disease process involving metabolic insult, chronic inflammation, and multiple immune mechanisms. Abs targeting apolipoprotein A-I (ApoA-I) have been found in patients with cardiovascular disease, autoimmune conditions, as well as those with no documented history of either. However, relatively little is known about how these Abs are generated and their relationship to diet and sex. In the current study, we modeled this aspect of autoimmunity using anti–ApoA-I immunization of male and female C57BL/6 mice. Unexpectedly, we found that autoantibodies directed against a single, previously unknown, epitope within the ApoA-I protein developed irrespective of immunization status or dyslipidemia in mice. When total IgG subclasses were analyzed over the course of time, we observed that rather than driving an increase in inflammatory IgG subclasses, consumption of Western diet suppressed age-dependent increases in IgG2b and IgG2c in male mice only. The lack of change observed in female mice suggested that diet and sex might play a combined role in Th1/Th2 balance and, ultimately, in immunity to pathogen challenge. This report demonstrates the need for inclusion of both sexes in studies pertaining to diet and aging and suggests that further study of immunogenic epitopes present in ApoA-I is warranted.
|Number of pages||9|
|State||Published - Aug 1 2020|
Bibliographical noteFunding Information:
Received for publication April 16, 2020. Accepted for publication July 14, 2020. Address correspondence and reprint requests to: Dr. Vincent J. Venditto, Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lee T. Todd Jr. Building, Room 337, 789 S. Limestone Street, Lexington, KY 40536-0596. E-mail address: firstname.lastname@example.org ORCIDs: 0000-0002-6698-3199 (M.G.P.); 0000-0003-3009-7686 (D.N.); 0000-0002-8808-4688 (C.M.I.); 0000-0002-4316-0587 (V.J.V.). This work was supported by the American Heart Association (17SDG32670001) and the National Institutes of Health (NIH) (P30GM127211, P20GM130456, R01HL152081). M.G.P. was supported by a training grant from the NIH (T32HL091812), D.N. was supported by a training grant from the National Center for Advancing Translational Sciences, NIH (TL1TR001997), and C.M.I. was supported by a Louis Stokes Alliance for Minority Participation scholarship, National Science Foundation (1826763). Abbreviations used in this article: ApoA-I, apolipoprotein A-I; CD, control diet; CHEMS, cholesteryl hemisuccinate; HDL, high-density lipoprotein; LDLr−/−, low-density lipoprotein receptor knockout; MPL, monophosphoryl lipid A; oxLDL, oxidized low-density lipoprotein; PBS-C, PBS containing 0.05% casein; RET, reciprocal end point titer; WD, Western diet. This article is distributed under the terms of the CC BY-NC-ND 4.0 Unported license. Copyright © 2020 The Authors
Copyright © 2020 The Authors
ASJC Scopus subject areas
- Immunology and Allergy