The inhibitory receptor toll interleukin-1R 8 (TIR8/IL-1R8/SIGIRR) is downregulated in chronic lymphocytic leukemia

Leuk Lymphoma. 2017 Oct;58(10):2419-2425. doi: 10.1080/10428194.2017.1295142. Epub 2017 Feb 28.


Toll interleukin-1 receptor 8 (also known as TIR8, SIGIRR, or IL1R8) is a transmembrane receptor that inhibits inflammation. Accordingly, genetic inactivation of this protein exacerbates chronic inflammation and inflammation-associated tumors in mice. In particular, lack of TIR8 triggers leukemia progression in a mouse model of chronic lymphocytic leukemia (CLL), supporting its role as a novel tumor restrainer. The aim of this study was to measure the amount of TIR8 mRNA and protein in CLL cells, and to analyze its regulation of expression. Circulating leukemic cells expressed lower levels of TIR8 compared to normal B-lymphocytes. Treatment of CLL cells with Azacytidine restored higher levels of TIR8 suggesting that DNA methylation may be involved in modulating TIR8 expression, with implications for novel therapeutic strategies.

Keywords: Azacytidine; SIGIRR; TIR8; Toll like receptors; chronic lymphocytic leukemia; toll interleukin-1 receptor 8.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic* / administration & dosage
  • Azacitidine* / administration & dosage
  • DNA Methylation
  • Disease Models, Animal
  • Humans
  • Inflammation
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell* / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell* / metabolism
  • Mice
  • Receptors, Interleukin-1* / metabolism


  • Antimetabolites, Antineoplastic
  • Receptors, Interleukin-1
  • SIGIRR protein, human
  • SIGIRR protein, mouse
  • Azacitidine