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The TIR8 receptor (also called SIGIRR) is an orphan member of the TIR superfamily. Its function is still elusive, but it is believed to trigger a negative pathway of regulation of the Toll-like/IL-1 receptor system, crucial for modulating inflammation in gastrointestinal (GI) tract and in other tissues (lung and kidney). The expression pattern of TIR8 in bovine tissues is unknown. Given the importance of GI diseases in cattle, the aim of this investigation was to study the distribution of TIR8 in a wide panel of non-pathologic tissues and organs. TIR8 expression was assessed by Northern blot analysis and further confirmed and comparatively quantified by qualitative and quantitative (Real-Time) PCR. The possible presence of tissue-specific isoforms was determined by Western blot immunodetection, using an anti-human TIR8 polyclonal antibody previously validated in bovine tissues. Similarly to humans and mice, bovine TIR8 was found in the GI tract and kidney. Expression of TIR8 mRNA was also detected in lymph nodes, thymus and thyroid gland. Interestingly, several isoforms of bovine TIR8 were detected in the same organs, suggesting the occurrence of different post-translational processings.

IL-1R/TLRs play an important role in the inflammatory responses. Their signaling pathway is tightly regulated to keep inflammation under control. The regulation involves both extracellular and intracellular mechanisms. TIR8, also known as SIGIRR (Single Immunoglobulin IL-1R-Related molecule), is an orphan receptor belonging to the IL-1R/TLRs super-family. Recent studies suggest its role in modulating the inflammatory response in the gastrointestinal tract in mice, acting as an IL-1 receptor family antagonist. We identified the sequence and analyzed the expression of TIR8 in a wide panel of organs and tissues in different animals. There was high homology of the cDNA sequence among human, mouse and the domestic species (74-85%). The pattern of expression of this receptor was similar in all the species examined (high levels in kidney and gastrointestinal tract) and similar to the human. These results demonstrate that TIR8 is conserved, in evolutionary terms, both with regard to sequence and pattern of expression, a finding consistent with a key function of this molecule in modulating inflammation in the gastrointestinal tract.

Expression pattern of the orphan receptor TIR8-SIGIRR in a few domestic animal species L. Turin & G. Tribbioli & F. Riva Published online: 8 August 2008 # Springer Science + Business Media B.V. 2008

Turin, L., Tribbioli, G., Invernizzi, P., Grati, F.R., Crema, S., Laible, G. and Riva, F., 2007. Fetal microchimerism in normal and embryo transfer bovine pregnancies. Veterinary Research Communications, 31(Suppl. 1), 205–207

Fetal cells and DNA have been detected in the maternal circulation during and after pregnancy in a few mammalian species. The incidence of similar microchimerism in cattle could have repercussion for the application of modern biotechnologies such as the transfer of transgenic embryos. To determine if feto-maternal leakage can occur in pregnant cows, we have analyzed maternal blood samples for the presence of fetal DNA during gestation and post-partum periods. Y chromosome-specific DNA was detected in up to 73% of blood samples from naturally mated heifers carrying conventional bull calves and a transgene-specific sequence in up to 50% of recipient cows carrying transgenic fetuses. These findings document for the first time that transplacental leakage of fetal DNA into the maternal circulation can occur in cattle despite the epitheliochorial placenta of ruminants, with potential implications for the utilization of recipient cows in the food chain.