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LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-γ, LPS and microbial infection

Abstract

Many genes in the central region of the major histocompatibility complex (MHC) encode proteins involved in immune and inflammatory responses. In this study, we have further characterized two genes in the MHC class IV region, leucocyte-specific transcript (LST) 1 and natural cytotoxicity-triggering receptor 3 (NCR3) (also known as 1C7 and natural killer (NK)p30). The specific function of LST1 is not known, although expression analysis and functional data suggest an immunomodulatory role. The LST1 gene undergoes extensive alternative splicing, giving rise to both membrane-bound (encoded by exon 3) and soluble isoforms. The NCR3 protein is involved in NK-mediated cytotoxicity and plays a role in NK/dendritic cell crosstalk. Expression of these genes was examined, by real-time reverse transcriptase–polymerase chain reaction, in autoimmune-induced inflammation, specifically rheumatoid-arthritis-affected blood and synovium, and in response to stimulation with inflammatory mediators and bacterial agents. The expression of LST1, specifically splice variants encoding soluble isoforms and NCR3, was increased in rheumatoid-arthritis-affected blood and synovium and was associated with more severe inflammation in the synovium. Furthermore, both genes were significantly up-regulated in response to lipopolysaccharide, interferon (IFN)-γ and bacterial infection. These findings suggest that NCR3 and soluble isoforms of LST1 may play a role in inflammatory and infectious diseases.

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Acknowledgements

We thank Pat Higgins for excellent technical assistance, J. Maxwell Dow for helpful discussions and all the participants in this study. We are grateful to Jim O'Mahony for advice on real-time RT-PCR analysis. This work was supported by a Research Scholarship from Enterprise Ireland (project code BR/2000/129) to H.M., the Health Research Board and ICARE Ireland, and in part by grants awarded by the Higher Education Authority of Ireland (PRTLI programmes to F.O.G.), The Science Foundation of Ireland (SFI 02/IN.1/B1261, 04/BR/B0597 to F.O.G.) and the European Commission (QLK3-CT-2000-31759, QLTK3-CT-2001-0010, and QLK5-CT-2002-0091 to F.O.G.).

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Correspondence to F. O'Gara.

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Mulcahy, H., O'Rourke, K.P., Adams, C. et al. LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-γ, LPS and microbial infection. Immunogenetics 57, 893–903 (2006). https://doi.org/10.1007/s00251-005-0057-2

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  • DOI: https://doi.org/10.1007/s00251-005-0057-2

Keywords

  • LST1
  • NCR3
  • Immunity
  • Rheumatoid arthritis