Haptoglobin deficiency facilitates the development of autoimmune inflammation.
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.
Galicia
Georgina
G
Division of Clinical Immunology, Gasthuisberg University Hospital, Catholic University of Leuven, Leuven, Belgium.
Maes
Wim
W
Verbinnen
Bert
B
Kasran
Ahmad
A
Bullens
Dominique
D
Arredouani
Mohamed
M
Ceuppens
Jan L
JL
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000276:immunology; D006242:Haptoglobins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics
D006023:Glycoproteins; D006242:Haptoglobins; D007074:Immunoglobulin G; D020381:Interleukin-17; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10; D007371:Interferon-gamma