Antibodies to MHC class II molecules induce autoimmunity: Critical role for macrophages in the immunopathogenesis of obliterative airway disease

Masashi Takenaka, Venkataswarup Tiriveedhi, Vijay Subramanian, Kiyotaka Hoshinaga, Alexander G. Patterson, Thalachallour Mohanakumar

研究成果: Article査読

22 被引用数 (Scopus)

抄録

Previous studies have shown that intrabronchial administration of antibodies (Abs) to MHC class I resulted in development of obliterative airway disease (OAD), a correlate of chronic human lung allograft rejection. Since development of Abs specific to mismatched donor HLA class II have also been associated with chronic human lung allograft rejection, we analyzed the role of Abs to MHC class II in inducing OAD. Administration of MHC class II Abs (M5/114) to C57BL/6 mice induced the classical features of OAD even though MHC class II expression is absent de novo on murine lung epithelial and endothelial cells. The induction of OAD was accompanied by enhanced cellular and humoral immune responses to self-antigens (Collagen V and K- α1Tubulin). Further, lung-infiltrating macrophages demonstrated a switch in their phenotype predominance from MΦ1 (F4/80+CD11c+) to MΦ2 (F4/80+CD206+) following administration of Abs and prior to development of OAD. Passive administration of macrophages harvested from animals with OAD but not from naïve animals induced OAD lesions. We conclude that MHC class II Abs induces a phenotype switch of lung infiltrating macrophages from MΦ1 (F4/80+CD11c+) to MΦ2 (F4/80+CD206+) resulting in the breakdown of self-tolerance along with an increase in autoimmune Th17 response leading to OAD.

本文言語English
論文番号e42370
ジャーナルPloS one
7
8
DOI
出版ステータスPublished - 10-08-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)
  • 農業および生物科学(全般)
  • 一般

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