Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR

Nadia Polentarutti, Giselle Penton Rol, Marta Muzio, Daniela Bosisio, Marco Camnasio, Federica Riva, Carla Zoja, Ariela Benigni, Susanna Tomasoni, Annunciata Vecchi, Cecilia Garlanda, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review


TIR8, also known as single Ig IL-1R-related molecule (SIGIRR), is a member of the IL-1 receptor family. The present study was designed to investigate the expression and function of TIR8. TIR8 was mainly expressed in mouse and human epithelial tissues such as kidney, lung and gut. Resting and activated T and B lymphocytes and monocytes-macrophages expressed little or no TIR8, with the exception of the mouse GG2EE macrophage line. In the kidney, the organ with highest mRNA levels, TIR8 expression was confined to epithelial cells and, in situ, to tubular epithelium. A variety of signals failed to regulate TIR8 expression, but LPS reduced TIR8 mRNA transcripts. An NF-kB driven reporter system was used to investigate the function of TIR8. TIR8 did not activate NF-kB expression alone or in concert with IL-1R1. In contrast, TIR8 inhibited signaling from the IL-1R complex. Inhibition required the intracellular portion of TIR8 but the extracellular domain was dispensable for blocking activity. Thus, TIR8 is a unique member of the IL-1R family, with a distinct pattern of epithelial expression, including the kidney and mucosae, and an inhibitory function on IL-1 signaling.

Original languageEnglish
Pages (from-to)211-218
Number of pages8
JournalEuropean Cytokine Network
Issue number4
Publication statusPublished - Oct 2003


  • Expression
  • IL-1R/TLRs
  • Signal transduction regulation
  • TIR8

ASJC Scopus subject areas

  • Immunology
  • Cell Biology


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