Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hilgendorf, I; Theurl, I; Gerhardt, LM; Robbins, CS; Weber, GF; Gonen, A; Iwamoto, Y; Degousee, N; Holderried, TA; Winter, C; Zirlik, A; Lin, HY; Sukhova, GK; Butany, J; Rubin, BB; Witztum, JL; Libby, P; Nahrendorf, M; Weissleder, R; Swirski, FK.
Innate response activator B cells aggravate atherosclerosis by stimulating T helper-1 adaptive immunity.
CIRCULATION. 2014; 129(16): 1677-1687.
Doi: 10.1161/CIRCULATIONAHA.113.006381
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- Co-Autor*innen der Med Uni Graz
- Zirlik Andreas
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- Abstract:
- Atherosclerotic lesions grow via the accumulation of leukocytes and oxidized lipoproteins in the vessel wall. Leukocytes can attenuate or augment atherosclerosis through the release of cytokines, chemokines, and other mediators. Deciphering how leukocytes develop, oppose, and complement each other's function and shape the course of disease can illuminate our understanding of atherosclerosis. Innate response activator (IRA) B cells are a recently described population of granulocyte macrophage colony-stimulating factor-secreting cells of hitherto unknown function in atherosclerosis. Here, we show that IRA B cells arise during atherosclerosis in mice and humans. In response to a high-cholesterol diet, IRA B cell numbers increase preferentially in secondary lymphoid organs via Myd88-dependent signaling. Mixed chimeric mice lacking B cell-derived granulocyte macrophage colony-stimulating factor develop smaller lesions with fewer macrophages and effector T cells. Mechanistically, IRA B cells promote the expansion of classic dendritic cells, which then generate interferon γ-producing T helper-1 cells. This IRA B cell-dependent T helper-1 skewing manifests in an IgG1-to-IgG2c isotype switch in the immunoglobulin response against oxidized lipoproteins. Granulocyte macrophage colony-stimulating factor-producing IRA B cells alter adaptive immune processes and shift the leukocyte response toward a T helper-1-associated milieu that aggravates atherosclerosis.
- Find related publications in this database (using NLM MeSH Indexing)
- Adaptive Immunity - genetics
- Animals -
- Atherosclerosis - genetics
- Atherosclerosis - immunology
- Atherosclerosis - pathology
- B-Lymphocytes - immunology
- B-Lymphocytes - pathology
- Bone Marrow Cells - immunology
- Bone Marrow Cells - pathology
- Cholesterol, Dietary - administration & dosage
- Cholesterol, Dietary - adverse effects
- Coculture Techniques -
- Humans -
- Immunity, Innate - genetics
- Lymphocyte Activation - genetics
- Lymphocyte Activation - immunology
- Male -
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Radiation Chimera -
- Th1 Cells - immunology
- Th1 Cells - pathology
- Find related publications in this database (Keywords)
- atherosclerosis
- B-lymphocytes
- dendritic cells
- granulocyte-macrophage colony-stimulating factor
- immunology
- T-lymphocytes