Hong-Xia Wang1, Wen-Jun Li1, Cui-Liu Hou1, Song Lai2, Yun-Long Zhang2, Cui Tian1, Hui Yang1, Jie Du2, Hui-Hua Li3. 1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. 2. Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China. 3. Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Abstract
Aims: CD1d is a member of the cluster of differentiation 1 (CD1) family of glycoproteins expressed on the surface of various antigen-presenting cells, which is recognized by natural killer T (NKT) cells. CD1d-dependent NKT cells play an important role in immune-mediated diseases; but the role of these cells in regulating cardiac remodelling remains unknown. Methods and results: Cardiac remodelling was induced by angiotensin (Ang) II infusion for 2 weeks. Ang II-induced increase in hypertension, cardiac performance, hypertrophy and fibrosis, inflammatory response, and activation of the NF-kB and TGF-β1/Smad2/3 pathways was significantly aggravated in CD1d knockout (CD1dko) mice compared with wild-type (WT) mice, but these effects were markedly abrogated in WT mice treated with α-galactosylceramide (αGC), a specific activator of NKT cells. Adoptive transfer of CD1dko bone marrow cells to WT mice further confirmed the deleterious effect of CD1dko. Moreover, IL-10 expression was significantly decreased in CD1dko hearts but increased in αGC-treated mice. Co-culture experiments revealed that CD1dko dendritic cells significantly reduced IL-10 mRNA expression from NKT cells. Administration of recombinant murine IL-10 to CD1dko mice improved hypertension, cardiac performance, and adverse cardiac remodelling induced by Ang II, and its cardioprotective effect was possibly associated with activation of STAT3, and inhibition of the TGF-β1 and NF-kB pathways. Conclusion: These findings revealed a previously undefined role for CD1d-dependent NKT cells in Ang II-induced cardiac remodelling, hence activation of NKT cells may be a novel therapeutic target for hypertensive cardiac disease.
Aims: CD1d is a member of the cluster of differentiation 1 (CD1) family of glycoproteins expressed on the surface of various antigen-presenting cells, which is recognized by natural killer T (NKT) cells. CD1d-dependent NKT cells play an important role in immune-mediated diseases; but the role of these cells in regulating cardiac remodelling remains unknown. Methods and results: Cardiac remodelling was induced by angiotensin (Ang) II infusion for 2 weeks. Ang II-induced increase in hypertension, cardiac performance, hypertrophy and fibrosis, inflammatory response, and activation of the NF-kB and TGF-β1/Smad2/3 pathways was significantly aggravated in CD1d knockout (CD1dko) mice compared with wild-type (WT) mice, but these effects were markedly abrogated in WT mice treated with α-galactosylceramide (αGC), a specific activator of NKT cells. Adoptive transfer of CD1dko bone marrow cells to WT mice further confirmed the deleterious effect of CD1dko. Moreover, IL-10 expression was significantly decreased in CD1dko hearts but increased in αGC-treated mice. Co-culture experiments revealed that CD1dko dendritic cells significantly reduced IL-10 mRNA expression from NKT cells. Administration of recombinant murineIL-10 to CD1dko mice improved hypertension, cardiac performance, and adverse cardiac remodelling induced by Ang II, and its cardioprotective effect was possibly associated with activation of STAT3, and inhibition of the TGF-β1 and NF-kB pathways. Conclusion: These findings revealed a previously undefined role for CD1d-dependent NKT cells in Ang II-induced cardiac remodelling, hence activation of NKT cells may be a novel therapeutic target for hypertensivecardiac disease.
Authors: Elisa Carrasco; Manuel M Gómez de Las Heras; Enrique Gabandé-Rodríguez; Gabriela Desdín-Micó; Juan Francisco Aranda; Maria Mittelbrunn Journal: Nat Rev Immunol Date: 2021-06-07 Impact factor: 53.106
Authors: Tomasz J Guzik; Saidi A Mohiddin; Anthony Dimarco; Vimal Patel; Kostas Savvatis; Federica M Marelli-Berg; Meena S Madhur; Maciej Tomaszewski; Pasquale Maffia; Fulvio D'Acquisto; Stuart A Nicklin; Ali J Marian; Ryszard Nosalski; Eleanor C Murray; Bartlomiej Guzik; Colin Berry; Rhian M Touyz; Reinhold Kreutz; Dao Wen Wang; David Bhella; Orlando Sagliocco; Filippo Crea; Emma C Thomson; Iain B McInnes Journal: Cardiovasc Res Date: 2020-08-01 Impact factor: 10.787