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Human disease mutations highlight the inhibitory function of TIM-3

A new study identifies loss-of-function mutations in HAVCR2, which encodes TIM-3, in patients with a rare cutaneous T cell lymphoma associated with aberrant immunological activation. These mutations lead to loss of the TIM-3 immunological checkpoint, thus promoting inflammation and malignancy.

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Fig. 1: TIM-3 deficiency leads to uncontrolled immunological activation resulting in T cell malignancy and autoinflammation.


  1. Gayden, T. et al. Nat. Genet. (2018).

    Article  PubMed  Google Scholar 

  2. Monney, L. et al. Nature 415, 536–541 (2002).

    Article  CAS  Google Scholar 

  3. Sabatos, C. A. et al. Nat. Immunol. 4, 1102–1110 (2003).

    Article  CAS  Google Scholar 

  4. Chiba, S. et al. Nat. Immunol. 13, 832–842 (2012).

    Article  CAS  Google Scholar 

  5. Fourcade, J. et al. J. Exp. Med. 207, 2175–2186 (2010).

    Article  CAS  Google Scholar 

  6. Jin, H. T. et al. Proc. Natl. Acad. Sci. USA 107, 14733–14738 (2010).

    Article  CAS  Google Scholar 

  7. Yan, J. et al. PLoS One 8, e58006 (2013).

    Article  CAS  Google Scholar 

  8. Sakuishi, K. et al. OncoImmunology 2, e23849 (2013).

    Article  Google Scholar 

  9. Dardalhon, V. et al. J. Immunol. 185, 1383–1392 (2010).

    Article  CAS  Google Scholar 

  10. Avery, L., Filderman, J., Szymczak-Workman, A. L. & Kane, L. P. Proc. Natl. Acad. Sci. USA 115, 2455–2460 (2018).

    Article  CAS  Google Scholar 

  11. Nakayama, M. et al. Blood 113, 3821–3830 (2009).

    Article  CAS  Google Scholar 

  12. Huang, Y. H. et al. Nature 536, 359 (2016).

    Article  CAS  Google Scholar 

  13. Zhu, C. et al. Nat. Immunol. 6, 1245–1252 (2005).

    Article  CAS  Google Scholar 

  14. Leitner, J. et al. PLoS Pathog. 9, e1003253 (2013).

    Article  CAS  Google Scholar 

  15. Hughes, R. C. Biochim. Biophys. Acta 1473, 172–185 (1999).

    Article  CAS  Google Scholar 

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Correspondence to Vijay K. Kuchroo.

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V.K.K. has patents dealing with intellectual property that have been licensed to Novartis Pharmaceuticals by the Brigham and Women’s Hospital.

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Dixon, K.O., Das, M. & Kuchroo, V.K. Human disease mutations highlight the inhibitory function of TIM-3. Nat Genet 50, 1640–1641 (2018).

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