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IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis

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 (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
organization
publishing date
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
Elsevier
external identifiers
  • scopus:85040538574
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
2018-11-21 21:38:16
@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},
  keyword      = {Atherosclerosis,IL-1,MyD88,T cells,Th17},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {180--187},
  publisher    = {Elsevier},
  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},
  volume       = {114},
  year         = {2018},
}