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CD11b+/Gr-1int monocytic myeloid derived suppressor cells contribute to high-fat induced inflammation and delayed tolerance in mouse liver (54.15)

Qifa Xie, Jingwen Zhang, Smita Ghare, Shirish Barve and Craig McClain
J Immunol April 1, 2011, 186 (1 Supplement) 54.15;
Qifa Xie
1Department of Medicine, University of Louisville, Louisville, KY
2Alcohol Research Center, University of Louisville, Louisville, KY
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Jingwen Zhang
1Department of Medicine, University of Louisville, Louisville, KY
2Alcohol Research Center, University of Louisville, Louisville, KY
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Smita Ghare
1Department of Medicine, University of Louisville, Louisville, KY
2Alcohol Research Center, University of Louisville, Louisville, KY
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Shirish Barve
1Department of Medicine, University of Louisville, Louisville, KY
2Alcohol Research Center, University of Louisville, Louisville, KY
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Craig McClain
1Department of Medicine, University of Louisville, Louisville, KY
2Alcohol Research Center, University of Louisville, Louisville, KY
3Veterans Affairs Medical Center, Louisville, KY
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Abstract

Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with universal expansion in nearly all inflammatory conditions. This study investigated the accumulation of MDSC in chronic inflammation and tolerance of obesity-related fatty liver disease. We found that the expansion of MDSC, specifically associated with the monocytic MDSC (M-MDSC): CD11b+Gr-1intLy6G-Ly6Chigh in the liver of B6 mice fed a high-fat diet contributes to liver inflammation and tolerance. M-MDSCs isolated from the liver of obese mice are more easily activated by way of Toll-like receptor (TLR4) stimulation resulting in inflammatory cytokine expression, and were functional MDSCs, readily inhibiting T cell proliferation in vitro dependent on cell-cell contact between MDSCs and T cells. The rapid accumulation of M-MDSC also contributed to delayed ConA tolerance in obesity-related fatty liver disease. M-MDSCs isolated from the liver of obese mice developed with ConA tolerance induce less liver regulatory T (Treg) cell expansion and less suppressing T cell proliferation in vitro. Experiments using mice depleted of Gr-1, or M- MDSC adoptive transfer demonstrated the important role of M-MDSC in liver inflammation and tolerance. These data unveil that M-MDSCs play an essential negative feedback function in liver immune homeostasis.

  • Copyright © 2011 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 186, Issue 1 Supplement
April 2011
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CD11b+/Gr-1int monocytic myeloid derived suppressor cells contribute to high-fat induced inflammation and delayed tolerance in mouse liver (54.15)
Qifa Xie, Jingwen Zhang, Smita Ghare, Shirish Barve, Craig McClain
The Journal of Immunology April 1, 2011, 186 (1 Supplement) 54.15;

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CD11b+/Gr-1int monocytic myeloid derived suppressor cells contribute to high-fat induced inflammation and delayed tolerance in mouse liver (54.15)
Qifa Xie, Jingwen Zhang, Smita Ghare, Shirish Barve, Craig McClain
The Journal of Immunology April 1, 2011, 186 (1 Supplement) 54.15;
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Print ISSN 0022-1767        Online ISSN 1550-6606