Lumican negatively controls the pathogenicity of murine encephalitic TH17 cells.
TH17 cells play an essential role in the development of both human multiple sclerosis and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, it is not well understood how the pathogenicity of TH17 cells is controlled in the autoimmune neuroinflammation. In vitro, we found Lumican (Lum), an extracellular matrix (ECM) protein, is selectively expressed by TH17 cells among tested murine TH subsets. Lum deficiency leads to earlier onset and enhanced severity of EAE. This enhanced disease in Lum-deficient mice is associated with increased production of IL-17 and IL-21 and decreased TH17 cell apoptosis. Dysregulation in cytokine production appears to be specific to TH17 cells as TH1 and TH2 cell polarization and/or cytokine production were unaltered. Furthermore, adoptive transfer of myelin oligodendrocyte glycoprotein specific TH17 cells derived from Lum-deficient mice led to earlier onset and increased severity of disease compared to controls highlighting a TH17-cell-intrinsic effect of Lum. Taken together, our results suggest that Lum negatively regulates encephalitic TH17 cells, implicating a potential therapeutic pathway in TH17 cell mediated autoimmune and inflammatory diseases.
Department of Molecular Genetics and Microbiology and Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Eliseo F
EF
Castillo
Department of Molecular Genetics and Microbiology and Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Handong
H
Zheng
Department of Molecular Genetics and Microbiology and Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Christian
C
Van Cabanlong
Deparment of Ophthalmology, University of Cincinnati, Cincinnati, OH, USA.
Fei
F
Dong
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Yan
Y
Luo
Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Yi
Y
Yang
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Meilian
M
Liu
Deparment of Ophthalmology, University of Cincinnati, Cincinnati, OH, USA.
Winston W-Y
WW
Kao
Department of Molecular Genetics and Microbiology and Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Xuexian O
XO
Yang
D000818:Animals; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006801:Humans; D000071234:Lumican / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D058408:Th1-Th2 Balance; D058504:Th17 Cells / Q000276:immunology*
C000604307:Lum protein, mouse; D000071234:Lumican; D063308:Myelin-Oligodendrocyte Glycoprotein
Apoptosis; Autoimmunity; Cytokine production; Lum; TH17
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