IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis
(2018) In Cardiovascular Research 114(1). p.180-187- Abstract
The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. Methods and results We transferred apoe-/-myd88\+/\+ or apoe-/-myd88-/- CD4+ T cells to T-A nd B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88\+/\+ CD4+ T cells. CD4+ T cells from... (More)
The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. Methods and results We transferred apoe-/-myd88\+/\+ or apoe-/-myd88-/- CD4+ T cells to T-A nd B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88\+/\+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-c. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. Conclusion We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels.
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- author
- Engelbertsen, Daniel LU ; Rattik, Sara LU ; Wigren, Maria LU ; Vallejo, Jenifer LU ; Marinkovic, Goran LU ; Schiopu, Alexandru LU ; Björkbacka, Harry LU ; Nilsson, Jan LU and Bengtsson, Eva LU
- organization
-
- EXODIAB: Excellence of Diabetes Research in Sweden
- EpiHealth: Epidemiology for Health
- Cardiovascular Research - Immunity and Atherosclerosis (research group)
- Rausing laboratory of Lund - Tumor section (research group)
- Cardiovascular Research - Cellular Metabolism and Inflammation (research group)
- Surgery (Lund)
- Cardiovascular Research - Matrix and Inflammation in Atherosclerosis (research group)
- publishing date
- 2018-01-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Atherosclerosis, IL-1, MyD88, T cells, Th17
- in
- Cardiovascular Research
- volume
- 114
- issue
- 1
- pages
- 8 pages
- publisher
- Oxford University Press
- external identifiers
-
- scopus:85040538574
- pmid:29036304
- ISSN
- 0008-6363
- DOI
- 10.1093/cvr/cvx196
- language
- English
- LU publication?
- yes
- id
- 15b15f28-30fc-4f56-890e-ad42d1d54f48
- date added to LUP
- 2018-02-23 19:25:54
- date last changed
- 2024-07-08 09:58:38
@article{15b15f28-30fc-4f56-890e-ad42d1d54f48, abstract = {{<p>The role of CD4<sup>+</sup> T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4<sup>+</sup> T cells in atherosclerosis. Methods and results We transferred apoe<sup>-/-</sup>myd88\+/\+ or apoe<sup>-/-</sup>myd88<sup>-/-</sup> CD4<sup>+</sup> T cells to T-A nd B-cell-deficient rag1<sup>-/-</sup>apoe<sup>-/-</sup> mice fed high fat diet. Mice given apoe<sup>-/-</sup>myd88<sup>-/-</sup> CD4<sup>+</sup> T cells exhibited reduced atherosclerosis compared with mice given apoe<sup>-/-</sup>myd88\+/\+ CD4<sup>+</sup> T cells. CD4<sup>+</sup> T cells from apoe<sup>-/-</sup>myd88<sup>-/-</sup> produced less IL-17 but similar levels of IFN-c. Treatment of human CD4<sup>+</sup> T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1<sup>-/-</sup> CD4<sup>+</sup> T cells recapitulated the phenotype seen by transfer of myd88<sup>-/-</sup> CD4<sup>+</sup> T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4<sup>+</sup> T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1<sup>-/-</sup> CD4<sup>+</sup> T cells. Conclusion We demonstrate that both IL1R and MyD88 signalling in CD4<sup>+</sup> T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels.</p>}}, author = {{Engelbertsen, Daniel and Rattik, Sara and Wigren, Maria and Vallejo, Jenifer and Marinkovic, Goran and Schiopu, Alexandru and Björkbacka, Harry and Nilsson, Jan and Bengtsson, Eva}}, issn = {{0008-6363}}, keywords = {{Atherosclerosis; IL-1; MyD88; T cells; Th17}}, language = {{eng}}, month = {{01}}, number = {{1}}, pages = {{180--187}}, publisher = {{Oxford University Press}}, series = {{Cardiovascular Research}}, title = {{IL-1R and MyD88 signalling in CD4<sup>+</sup> T cells promote Th17 immunity and atherosclerosis}}, url = {{http://dx.doi.org/10.1093/cvr/cvx196}}, doi = {{10.1093/cvr/cvx196}}, volume = {{114}}, year = {{2018}}, }