Enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesis
IntroductionInnate lymphoid cells (ILCs) have been implicated in multiple pathologic conditions, including atherogenesis, as documented in experimental mice studies, however, their role in atherosclerosis in humans remains unexplored.MethodsHere, we identify ILCs and their dynamics in early, advance...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1354617/full |
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| author | Kartika R. Pertiwi Kartika R. Pertiwi Marcel B. M. Teunissen Gabrielle Krebbers Martine C.M. Willems Martine C.M. Willems Laurens Huisman Laurens Huisman Cindy Poelen Allard C. van der Wal Onno J. de Boer |
| author_facet | Kartika R. Pertiwi Kartika R. Pertiwi Marcel B. M. Teunissen Gabrielle Krebbers Martine C.M. Willems Martine C.M. Willems Laurens Huisman Laurens Huisman Cindy Poelen Allard C. van der Wal Onno J. de Boer |
| author_sort | Kartika R. Pertiwi |
| collection | DOAJ |
| description | IntroductionInnate lymphoid cells (ILCs) have been implicated in multiple pathologic conditions, including atherogenesis, as documented in experimental mice studies, however, their role in atherosclerosis in humans remains unexplored.MethodsHere, we identify ILCs and their dynamics in early, advanced, and complicated human carotid- and aortic atherosclerotic plaques, using a multiplex immunohistochemical quadruple-staining technique with prototypic transcription factors T-bet, GATA3, or RORgt for identification of the ILC1, ILC2 and ILC3 subsets, respectively, in combination with lineage markers CD3, CD20/ CD79a and CD56 to exclude other lymphoid cell types. ILC subsets were quantified, and to put this in perspective, their numbers were expressed as percentage of the total number of infiltrated lymphoid cells and related to the frequency of conventional T cells, B cells, NK cells, and NKT cells. ResultsAll ILC subsets were present in every different stage of atherogenesis. ILC1s were the most abundant ILC subset, and their numbers significantly increased in the course of plaque development, but paradoxically, their relative frequency was reduced because of a higher increment of T cells and B cells. The numbers of ILC2s and ILC3s also gradually increased, but this trend did not achieve significance. T cell subsets always significantly outnumbered their ILC counterparts, except for the early lesions where the proportion of ILC1s was markedly higher, albeit not significant. DiscussionThe high abundance of ILC1s in the early stages and further significant enrichment in later stages, suggest they may participate in the initiation and development of atherogenesis, and thus, may represent a novel target to prevent or treat atherosclerosis. |
| first_indexed | 2024-04-24T13:52:25Z |
| format | Article |
| id | doaj.art-4d9ca244153d4cf8b8cbf3794bc01946 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T13:52:25Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4d9ca244153d4cf8b8cbf3794bc019462024-04-04T04:26:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.13546171354617Enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesisKartika R. Pertiwi0Kartika R. Pertiwi1Marcel B. M. Teunissen2Gabrielle Krebbers3Martine C.M. Willems4Martine C.M. Willems5Laurens Huisman6Laurens Huisman7Cindy Poelen8Allard C. van der Wal9Onno J. de Boer10Department of Pathology, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsFaculty of Medicine and Department of Biology Education, Faculty of Mathematics and Natural Science, Universitas Negeri Yogyakarta, Yogyakarta, IndonesiaDepartment of Dermatology, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Dermatology, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Vascular Surgery, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Vascular Surgery, Flevoziekenhuis, Almere, NetherlandsDepartment of Vascular Surgery, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Vascular Surgery, Flevoziekenhuis, Almere, NetherlandsDepartment of Pathology, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Pathology, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Pathology, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsIntroductionInnate lymphoid cells (ILCs) have been implicated in multiple pathologic conditions, including atherogenesis, as documented in experimental mice studies, however, their role in atherosclerosis in humans remains unexplored.MethodsHere, we identify ILCs and their dynamics in early, advanced, and complicated human carotid- and aortic atherosclerotic plaques, using a multiplex immunohistochemical quadruple-staining technique with prototypic transcription factors T-bet, GATA3, or RORgt for identification of the ILC1, ILC2 and ILC3 subsets, respectively, in combination with lineage markers CD3, CD20/ CD79a and CD56 to exclude other lymphoid cell types. ILC subsets were quantified, and to put this in perspective, their numbers were expressed as percentage of the total number of infiltrated lymphoid cells and related to the frequency of conventional T cells, B cells, NK cells, and NKT cells. ResultsAll ILC subsets were present in every different stage of atherogenesis. ILC1s were the most abundant ILC subset, and their numbers significantly increased in the course of plaque development, but paradoxically, their relative frequency was reduced because of a higher increment of T cells and B cells. The numbers of ILC2s and ILC3s also gradually increased, but this trend did not achieve significance. T cell subsets always significantly outnumbered their ILC counterparts, except for the early lesions where the proportion of ILC1s was markedly higher, albeit not significant. DiscussionThe high abundance of ILC1s in the early stages and further significant enrichment in later stages, suggest they may participate in the initiation and development of atherogenesis, and thus, may represent a novel target to prevent or treat atherosclerosis. https://www.frontiersin.org/articles/10.3389/fimmu.2024.1354617/fullinnate lymphoid cellsatherosclerosisinnate immunityinflammationlymphocytesimmunohistochemistry |
| spellingShingle | Kartika R. Pertiwi Kartika R. Pertiwi Marcel B. M. Teunissen Gabrielle Krebbers Martine C.M. Willems Martine C.M. Willems Laurens Huisman Laurens Huisman Cindy Poelen Allard C. van der Wal Onno J. de Boer Enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesis Frontiers in Immunology innate lymphoid cells atherosclerosis innate immunity inflammation lymphocytes immunohistochemistry |
| title | Enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesis |
| title_full | Enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesis |
| title_fullStr | Enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesis |
| title_full_unstemmed | Enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesis |
| title_short | Enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesis |
| title_sort | enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesis |
| topic | innate lymphoid cells atherosclerosis innate immunity inflammation lymphocytes immunohistochemistry |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1354617/full |
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