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Haptoglobin deficiency facilitates the development of autoimmune inflammation.

Abstract
Haptoglobin (HP) is an acute phase protein synthesized by liver cells in response to IL-6. HP has been demonstrated to modulate the immune response and to have anti-inflammatory activities. To analyze HP's effect on autoimmune inflammation, we here studied the course of EAE induced by immunization of Hp knockout (Hp(-/-)) and syngeneic WT mice with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)). Hp(-/-)mice suffered from a more severe disease that was associated with increased expression of IL-17A, IL-6, and IFN-gamma mRNA in the CNS and with a denser cellular infiltrate in the spinal cord. During the recovery phase, a significantly higher number of myeloid DC, CD8+ cells, IL-17+ CD4+ and IFN-gamma+ CD4+ cells persisted in the CNS of Hp(-/-) mice. Absence of HP affected the priming and differentiation of T cells after MOG(35-55) immunization, as levels of Th2 cytokines produced in response to MOG stimulation by Hp(-/-) T cells were reduced. These results suggest that HP plays a modulatory and protective role on autoimmune inflammation of the CNS.
AuthorsGeorgina Galicia, Wim Maes, Bert Verbinnen, Ahmad Kasran, Dominique Bullens, Mohamed Arredouani, Jan L Ceuppens
JournalEuropean journal of immunology (Eur J Immunol) Vol. 39 Issue 12 Pg. 3404-12 (Dec 2009) ISSN: 1521-4141 [Electronic] Germany
PMID19795414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Glycoproteins
  • Haptoglobins
  • Immunoglobulin G
  • Interleukin-17
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Transforming Growth Factor beta
  • myelin oligodendrocyte glycoprotein (35-55)
  • Interleukin-10
  • Interferon-gamma
Topics
  • Animals
  • Autoimmune Diseases (genetics, immunology, metabolism)
  • Brain (immunology, metabolism, pathology)
  • Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, metabolism)
  • Enzyme-Linked Immunosorbent Assay
  • Glycoproteins (immunology)
  • Haptoglobins (deficiency, genetics, metabolism)
  • Immunization
  • Immunoglobulin G (blood)
  • Inflammation (genetics, immunology, metabolism)
  • Interferon-gamma (genetics, metabolism)
  • Interleukin-10 (genetics)
  • Interleukin-17 (genetics)
  • Lymph Nodes (metabolism, pathology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myelin Proteins
  • Myelin-Associated Glycoprotein (chemistry, immunology)
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments (immunology)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord (immunology, metabolism, pathology)
  • Spleen (metabolism, pathology)
  • T-Lymphocytes (immunology, metabolism, pathology)
  • Th2 Cells (metabolism)
  • Transforming Growth Factor beta (genetics)

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