Immature muscle precursors are a source of interferon-β in myositis: Role of Toll-like receptor 3 activation and contribution to HLA class I up-regulation
✍ Scribed by Anne Tournadre; Vanina Lenief; Assia Eljaafari; Pierre Miossec
- Publisher
- John Wiley and Sons
- Year
- 2012
- Tongue
- English
- Weight
- 613 KB
- Volume
- 64
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
Abstract
Objective
To investigate the production of type I interferon (IFN) by myoblasts and to identify its cell source and the link to Toll‐like receptor (TLR) and C‐type lectin receptor (CLR) expression and function in myositis biopsy sections.
Methods
Production of IFNβ was assessed in cultured myoblasts after stimulation with the TLR‐3 agonist poly(I‐C) or with cytokines involved in Th1 and Th17 differentiation. Expression of HLA class I molecules by myoblasts was analyzed by fluorescence‐activated cell sorting after activation of TLR‐3 and IFNβ neutralization. In muscle biopsy samples from patients with polymyositis or dermatomyositis, expression of IFNβ, CD56 (a marker of immature muscle precursors), and HLA class I was analyzed using immunohistochemistry. Inflammatory infiltrates were characterized for the expression of myeloid dendritic cells (DCs), their associated CLRs, and the products of activated DCs, interleukin‐12 (IL‐12), and IL‐23.
Results
In cultured myoblasts, stimulation of TLR‐3 induced the production of IFNβ when combined with IFNγ and up‐regulated the expression of HLA class I molecules, which was decreased after IFNβ blockade. In myositis biopsy tissues, immature muscle precursors overexpressing HLA class I were identified as a source of IFNβ. CLRs associated with myeloid DCs were broadly expressed in inflammatory infiltrates, in association with IL‐12 and IL‐23, and with immature muscle precursors.
Conclusion
Immature muscle precursors may represent a local source of IFNβ and the target of an immune response involving activated DCs associated with the expression of CLRs and of IL‐12 and IL‐23, which are implicated in T cell polarization. In turn, such local production of IFNβ after TLR‐3 activation in the presence of the Th1 cytokine IFNγ may explain HLA class I overexpression in myositis.