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TLR4/MyD88-induced CD11b+Gr-1 int F4/80+ non-migratory myeloid cells suppress Th2 effector function in the lung.

Abstract
In humans, environmental exposure to a high dose of lipopolysaccharide (LPS) protects from allergic asthma, the immunological underpinnings of which are not well understood. In mice, exposure to a high LPS dose blunted house dust mite-induced airway eosinophilia and T-helper 2 (Th2) cytokine production. Although adoptively transferred Th2 cells induced allergic airway inflammation in control mice, they were unable to do so in LPS-exposed mice. LPS promoted the development of a CD11b(+)Gr1(int)F4/80(+) lung-resident cell resembling myeloid-derived suppressor cells in a Toll-like receptor 4 and myeloid differentiation factor 88 (MyD88)-dependent manner that suppressed lung dendritic cell (DC)-mediated reactivation of primed Th2 cells. LPS effects switched from suppressive to stimulatory in MyD88(-/-) mice. Suppression of Th2 effector function was reversed by anti-interleukin-10 (IL-10) or inhibition of arginase 1. Lineage(neg) bone marrow progenitor cells could be induced by LPS to develop into CD11b(+)Gr1(int)F4/80(+)cells both in vivo and in vitro that when adoptively transferred suppressed allergen-induced airway inflammation in recipient mice. These data suggest that CD11b(+)Gr1(int)F4/80(+) cells contribute to the protective effects of LPS in allergic asthma by tempering Th2 effector function in the tissue.
AuthorsM Arora, S L Poe, T B Oriss, N Krishnamoorthy, M Yarlagadda, S E Wenzel, T R Billiar, A Ray, P Ray
JournalMucosal immunology (Mucosal Immunol) Vol. 3 Issue 6 Pg. 578-93 (Nov 2010) ISSN: 1935-3456 [Electronic] United States
PMID20664577 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Blocking
  • Antigens, Differentiation
  • CD11b Antigen
  • Lipopolysaccharides
  • Myeloid Differentiation Factor 88
  • monocyte-macrophage differentiation antigen
  • Interleukin-10
Topics
  • Adoptive Transfer
  • Animals
  • Antibodies, Blocking (administration & dosage)
  • Antigens, Differentiation (biosynthesis)
  • CD11b Antigen (biosynthesis)
  • Cell Differentiation (drug effects)
  • Cell Movement (drug effects)
  • Cells, Cultured
  • Eosinophilia
  • Humans
  • Hypersensitivity (immunology, physiopathology, therapy)
  • Immunosuppression Therapy
  • Interleukin-10 (immunology)
  • Lipopolysaccharides (administration & dosage)
  • Lung (drug effects, immunology, metabolism, pathology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myeloid Cells (drug effects, immunology, metabolism, pathology)
  • Myeloid Differentiation Factor 88 (genetics, immunology, metabolism)
  • Pyroglyphidae (immunology)
  • Th2 Cells (drug effects, immunology, metabolism, pathology)

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