Development of atherosclerotic lesion in mice deficient for both CD1d- and MR1-restricted NKT cells — ASN Events
  1. Schedule
  2. Session 10 - Autoimmunity/Cancer I
  3. Development of atherosclerotic lesion in mice deficient for both CD1d- and MR1-restricted NKT cells

Development of atherosclerotic lesion in mice deficient for both CD1d- and MR1-restricted NKT cells (#76)

Koki Fujita 1 , Masashi Sato 1 , Miyuki Hoshino 1 , Kentaro Shimano 1 , Koji Eshima 1 , Susan Gilfillan 2 , Sachiko Miyake 3 , Luc Van Kaer 4 , Takashi Yamamura 5 , Kazuya Iwabuchi 1
  1. Kitasato University School of Medicine, Sagamihara, KANAGAWA, Japan
  2. Dept Pathol Immunol , Washington Univ Med Sch, Washington, MO, USA
  3. Dept Immunol, Juntendo Univ Med Sch, Tokyo
  4. Dept Microbiol Immunol , Vanderbilt Univ Med Sch, Nashville, TN,, USA
  5. Dept Immunol, Inst Neurosci, Tokyo, NCNP, Japan
We have studied lesion development of atherosclerosis in apoE-/- mice also deficient in NKT-cell subsets. Lesion development is suppressed in CD1d-/-apoE-/- double knockout (CD1d-DKO) mice that lack all CD1d-restricted NKT (NKT for simplicity) cells including invariant NKT (iNKT cells) (2004 Heron Island), whereas the development is enhanced in MR1-/-apoE-/- double knockout (MR1-DKO) mice where MR1-restricted NKT (MAIT) cells are deficient (2013 Tour), suggesting that CD1d-restricted NKT cells are pro-atherogenic and MAIT cells are anti-atherogenic. The latter, MR1-DKO mice retain CD1d-restricted NKT cells that play a pro-atherogenic role.  In order to pursue a mechanism for aggravation of atherosclerotic lesion in MR1-DKO mice, we examined whether a removal of NKT cells may reduce the lesion area by establishing CD1d-/-MR1-/-apoE-/- triple knockout (TKO) mice and comparing the lesion size to that of MR1-DKO mice.  However, the lesion development was not reduced but appeared enhanced in TKO than that of MR1-DKO mice in the absence of both CD1d- and MR1-restricted NKT cells.  The cholesterol level was comparable between MR1-DKO and TKO, suggesting that dyslipidemia is not a primary cause of difference. The expression of IL-6, TNF-a and MCP-1 was higher in TKO than in MR1-DKO, which was consistent with the above finding.  Small but significant proportion of NK1.1+TCRb+ T cells remained undeleted in TKO mice, which may aggravate atherogenesis.  The remaining NK1.1+TCRb+ cells in TKO showed slightly different Vb usage and different pattern of cytokine production.  A mechanism how the atherosclerotic lesion is developed and aggravated in the absence of NKT and MAIT cells in TKO is now underway.