Hypercholesterolemia induces a mast cell–CD4+ T cell interaction in atherosclerosis

Kritikou, E., van der Heijden, T., Swart, M., van Duijn, J., Slütter, B., Wezel, A., Smeets, H. J., Maffia, P. , Kuiper, J. and Bot, I. (2019) Hypercholesterolemia induces a mast cell–CD4+ T cell interaction in atherosclerosis. Journal of Immunology, 202(5), pp. 1531-1539. (doi: 10.4049/jimmunol.1800648) (PMID:30683705)

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Mast cells (MCs) are potent innate immune cells that aggravate atherosclerosis through the release of proinflammatory mediators inside atherosclerotic plaques. Similarly, CD4+ T cells are constituents of the adaptive immune response and accumulate within the plaques following lipid-specific activation by APCs. Recently it has been proposed that these two cell types can interact in a direct manner. However, no indication of such an interaction has been investigated in the context of atherosclerosis. In our study, we aimed to examine whether MCs can act as APCs in atherosclerosis, thereby modulating CD4+ T cell responses. We observed that MCs increased their MHC class II expression under hyperlipidemic conditions both in vivo and in vitro. Furthermore, we showed that MCs can present Ags in vivo via MHC class II molecules. Serum from high-fat diet–fed mice also enhanced the expression of the costimulatory molecule CD86 on cultured MCs, whereas OVA peptide–loaded MCs increased OT-II CD4+ T cell proliferation in vitro. The aortic CD4+ and TH1 cell content of atherosclerotic mice that lack MCs was reduced as compared with their wild-type counterparts. Importantly, we identified MCs that express HLA-DR in advanced human atheromata, indicating that these cells are capable of Ag presentation within human atherosclerotic plaques. Therefore, in this artice, we show that MCs may directly modulate adaptive immunity by acting as APCs in atherosclerosis.

Item Type:Articles
Additional Information:This work was supported by a Dr. Dekker Senior Postdoc grant from the NetherlandsHeart Foundation (2012T083 to E.K. and I.B.). This work was also supported by theNetherlands CardioVascular Research Initiative: The Dutch Heart Foundation, theDutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences,for the GENIUS project “Generating the Best Evidence-Based PharmaceuticalTargets for Atherosclerosis” (CVON2011-19). P.M. is supported by British HeartFoundation Grants PG/12/81/29897 and RE/13/5/30177.
Glasgow Author(s) Enlighten ID:Maffia, Professor Pasquale
Authors: Kritikou, E., van der Heijden, T., Swart, M., van Duijn, J., Slütter, B., Wezel, A., Smeets, H. J., Maffia, P., Kuiper, J., and Bot, I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN (Online):1550-6606
Published Online:25 January 2019

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
614711Defining innate and adaptive immune functions of plasmacytoid dendritic cells in atherosclerosis.Pasquale MaffiaBritish Heart Foundation (BHF)PG/12/81/29897III -IMMUNOLOGY
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES