Yanick Crow

Laboratory of neurogenetics and neuroinflammation

Yanick Crow
  • Mathieu Rodero
  • Yoann Rose
  • Isabelle Melki
  • Carolina Uggenti
  • Naoki Kitabayashi
  • Marie-Louise Frémond

Meilleures publications

Frémond ML. Efficacy of the janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in three children. J Allergy Clin Immunol. 2016 Dec;138(6):1752-1755.


Jenkinson EM. Mutations in SNORD118 cause cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nat Genet. 2016 Oct;48(10):1185-92


CROW YJ, Aicardi-Goutières syndrome and the type I interferonopathies. Nat Rev Immunol 2015;15:429-40.


RICE GI et al. Gain of function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signalling. Nat Genet 2014;46:503-9.


RICE GI et al. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurology 2013;12:1159-69.


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Laboratory of neurogenetics and neuroinflammation

 

Members of the laboratory: Mathieu Rodero (post-doc); Yoann Rose (ingenieur); Anais Boulai (ingenieur); Isabelle Melki (PhD student - MD); Yanick Crow (head)

 

Our work has concentrated on the Mendelian inflammatory disorder Aicardi-Goutières syndrome (AGS). Clinical and genetic studies of this severe disease have helped to define a cell-intrinsic mechanism for the initiation of autoinflammation / autoimmunity by interferon-stimulatory nucleic acids, and have further emphasised the importance of type I interferon metabolism in the pathogenesis of certain non-Mendelian disorders, particularly systemic lupus erythematosus. A combination of clinical, genetic and immunological perspectives have led us to suggest that monogenic disorders associated with an upregulation of type I interferons represent a novel set of inborn errors of immunity due to abnormal sensing, inappropriate stimulation, or defective negative regulation of the type I interferon system – the so-called type I interferonopathies (Figure). This concept immediately suggests the possibility of ‘anti-interferon’ / ‘anti-inflammatory’ therapies, and has important implications for fundamental research into mechanisms of self / non-self discrimination and viral immunity.

 

 

 

Possible mechanisms leading to a type I interferonopathy

1. Inappropriate stimulation of the type I interferon response machinery due to an abnormal accumulation of an endogenous nucleic acid ligand

2. Inappropriate stimulation of the type I interferon response machinery due to a change in the composition of an endogenous nucleic acid ligand

3. Enhanced sensitivity or ligand-independent (constitutive) activation of a nucleic acid receptor signalling to the type I interferon pathway

4. Enhanced sensitivity or ligand-independent (constitutive) activation of a non-nucleic acid receptor component (e.g. an adaptor molecule) of the interferon-signalling pathway

5. Defective negative regulation of a nucleic-acid dependent type I interferon response

6. Mutations in other genes involved in non-nucleic acid related stimulation / regulation of the type I interferon pathway (including components of the adaptive immune response)