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iRHOM2 takes control of rheumatoid arthritis

Stefan F Lichtenthaler1

  • 1German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. stefan.lichtenthaler@dzne.de

The Journal of Clinical Investigation
|January 26, 2013
PubMed

Insights

Researchers identified iRHOM2 as a key activator of TNF-α convertase (TACE) in immune cells. Inhibiting iRHOM2 protected mice from inflammatory arthritis, suggesting it as a potential therapeutic target for rheumatoid arthritis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Drug Discovery

Background:

  • Rheumatoid arthritis is an inflammatory joint disorder driven by the cytokine TNF-α.
  • TNF-α convertase (TACE) releases TNF-α, making it a therapeutic target.
  • Broad TACE inhibition is problematic due to its role in development and cancer.

Purpose of the Study:

  • To identify specific activators of TACE in immune cells.
  • To evaluate iRHOM2 as a potential drug target for inflammatory arthritis.

Main Methods:

  • Investigated the role of iRHOM2 in TACE activation within immune cells.
  • Assessed the therapeutic potential of targeting iRHOM2 in a mouse model of inflammatory arthritis.

Main Results:

  • iRHOM2 was identified as a crucial activator of TACE in immune cells.
  • Loss of iRHOM2 function significantly protected mice from developing inflammatory arthritis.

Conclusions:

  • iRHOM2 is a critical regulator of TACE activity in immune cells.
  • iRHOM2 represents a promising, tissue-specific drug target for rheumatoid arthritis treatment.

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