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Macrophages driven to a novel state of activation have anti-inflammatory properties in mice.

Publication ,  Journal Article
Brem-Exner, BG; Sattler, C; Hutchinson, JA; Koehl, GE; Kronenberg, K; Farkas, S; Inoue, S; Blank, C; Knechtle, SJ; Schlitt, HJ; Fändrich, F ...
Published in: J Immunol
January 1, 2008

Recurrent episodes of inflammation underlie numerous pathologies, notably those of inflammatory bowel diseases. In this study, we describe a population of macrophages in a novel state of activation that mitigates colitis in mice. The cells responsible for this effect, called IFN-gamma-stimulated monocyte-derived cells (IFNgamma-MdC), derive from mouse spleen, blood, and bone marrow monocytes and are distinguished from known macrophage populations by mode of generation, cell surface phenotype, and function. IFNgamma-MdC only arise when macrophages are cultivated in the presence of CD40L-expressing CD4+ T cells, M-CSF, and IFN-gamma. IFNgamma-MdC express markers including F4/80, CD11b/c, CD86, and CD274; they are negative for CD4, CD8, Gr1, CD19, CD80, and CD207. Functionally, IFNgamma-MdC are defined by their capacity to enrich cocultured T cell populations for CD4+CD25+Foxp3+ regulatory cells; this enrichment, constituting up to 60% or more of residual lymphocytes, is attributed to an expansion, but also to a cell contact and caspase-dependent depletion of activated T cells. In mice, IFNgamma-MdC delivered i.v. traffic to gut-associated peripheral lymphoid tissues, including the mesenteric lymph nodes, Peyer's patches, and colonic mucosa, and promote the clinical and histological resolution of chronic colitis. We conclude that IFNgamma-MdC represent macrophages in a novel state of activation, possessing multiple T cell-suppressive effects with therapeutic potential for the treatment of autoimmune inflammation.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

January 1, 2008

Volume

180

Issue

1

Start / End Page

335 / 349

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Receptors, Interferon
  • Monocytes
  • Mice, Inbred BALB C
  • Mice
  • Mesentery
  • Macrophages
  • Macrophage Activation
  • Lymphocytes
  • Lymph Nodes
 

Citation

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Brem-Exner, B. G., Sattler, C., Hutchinson, J. A., Koehl, G. E., Kronenberg, K., Farkas, S., … Geissler, E. K. (2008). Macrophages driven to a novel state of activation have anti-inflammatory properties in mice. J Immunol, 180(1), 335–349. https://doi.org/10.4049/jimmunol.180.1.335
Brem-Exner, Beate G., Christine Sattler, James A. Hutchinson, Gudrun E. Koehl, Katharina Kronenberg, Stefan Farkas, Seiichiro Inoue, et al. “Macrophages driven to a novel state of activation have anti-inflammatory properties in mice.J Immunol 180, no. 1 (January 1, 2008): 335–49. https://doi.org/10.4049/jimmunol.180.1.335.
Brem-Exner BG, Sattler C, Hutchinson JA, Koehl GE, Kronenberg K, Farkas S, et al. Macrophages driven to a novel state of activation have anti-inflammatory properties in mice. J Immunol. 2008 Jan 1;180(1):335–49.
Brem-Exner, Beate G., et al. “Macrophages driven to a novel state of activation have anti-inflammatory properties in mice.J Immunol, vol. 180, no. 1, Jan. 2008, pp. 335–49. Pubmed, doi:10.4049/jimmunol.180.1.335.
Brem-Exner BG, Sattler C, Hutchinson JA, Koehl GE, Kronenberg K, Farkas S, Inoue S, Blank C, Knechtle SJ, Schlitt HJ, Fändrich F, Geissler EK. Macrophages driven to a novel state of activation have anti-inflammatory properties in mice. J Immunol. 2008 Jan 1;180(1):335–349.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

January 1, 2008

Volume

180

Issue

1

Start / End Page

335 / 349

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Receptors, Interferon
  • Monocytes
  • Mice, Inbred BALB C
  • Mice
  • Mesentery
  • Macrophages
  • Macrophage Activation
  • Lymphocytes
  • Lymph Nodes