Th1 and Th17 balance in inflammatory myopathies: interaction with dendritic cells and possible link with response to high-dose immunoglobulins.
To clarify the interactions between dendritic cells (DCs) and Th1 and Th17 T cell subsets and the mode of action of IVIG in inflammatory myopathies, Expression of CD4(+) and CD8(+) T cells, immature (CD1a) and mature (DC-LAMP) DCs, interleukin-17 (IL-17) and interferon-gamma (IFN-gamma), was quantified by immunohistochemistry in muscle biopsies from 13 patients (11 with polymyositis (PM) and 2 dermatomyositis (DM)) obtained before treatment with IVIG. The Th1/Th17 cytokine and the immature/mature DC ratio were studied according to the response to IVIG. Immature DCs were rarely detected compared to mature DCs, observed in all samples except one PM. IFN-gamma-producing cell count was higher than IL-17 count. Neither the expression of IFN-gamma nor IL-17 was correlated with that of DC subsets. Seven of the 13 patients (6 PM and 1 DM) responded to IVIG. T cells and DC subsets were not differentially expressed between responders and non-responders. The frequency of IFN-gamma-producing cells was significantly higher in non-responders with an increased IFN-gamma/IL-17-producing-cell ratio. In conclusion, mature rather than immature DC and IFN-gamma-rather than IL-17-producing cells accumulate in inflamed muscle. Increased IFN-gamma-producing cell count and IFN-gamma/IL-17-ratio were found in IVIG non-responders, suggesting a role for the Th17 mediated pathway in the response to IVIG.
Tournadre
Anne
A
Department of Immunology and Rheumatology, Clinical Immunology Unit, Hospital Edouard Herriot, University of Lyon, Hospices Civils de Lyon, 69437 Lyon Cedex 03, France.
Porcherot
Marine
M
Chérin
Patrick
P
Marie
Isabelle
I
Hachulla
Eric
E
Miossec
Pierre
P
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D003713:Dendritic Cells / Q000276:immunology*; D003882:Dermatomyositis / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology / Q000276:immunology / Q000473:pathology; D009220:Myositis / Q000188:drug therapy / Q000276:immunology; D017285:Polymyositis / Q000188:drug therapy / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D055815:Young Adult
D016756:Immunoglobulins, Intravenous; D020381:Interleukin-17; D007371:Interferon-gamma