Regulation of STING through UNC93B1-STIM1 association and its impact in autoimmunity

Responsable du Stage : Bénédicte Manoury

Tél : 0140615382 Fax : 0140615385 E-mail:

Institut Necker Enfants Malades

Résumé du Projet de Stage 

UNC93B1, a highly conserved 12-membrane spanning molecule residing in the endoplasmic reticulum (ER), has been identified as a key regulator in the trafficking1 and folding2 to endosomes of intracellular Toll-like receptors (TLRs) that detect microbial nucleic acids. Indeed, a mutation in the Unc93b1 gene (3d mutation) results in inhibition of intracellular TLRs signalling in dendritic cells (DCs). We have shown that UNC93B1, but not the 3d mutant, also binds the Ca2+ sensor stromal interaction molecule 1 or STIM1 in the ER3 and that this association is essential for antigen cross presentation3,4. Recently the group of  Gwack5 has demonstrated abnormal localisation of STING (stimulator of interferon genes) in cells deficient for STIM1, resulting in enhanced type I interferon secretion at the steady state. Indeed, STIM1 is required for STING localisation in the ER and the absence of STIM1 triggers  STING trafficking to the Golgi apparatus and its activation. STING in a protein critical for type I interferon response to pathogens containing DNA and its abnormal activation is associated to inflammation and autoimmunity. Our preliminary data indicate a role for UNC3B1 in STING localisation and signaling. Thus, this project aims at studying the role of UNC93B1 in STING trafficking and activation in DCs and its link in autoimmunity and inflammatory diseases.

  1. Lee BL et al, 2013. Elife 19;2:e00291.
  2. Pelka K et al, 2018. Immunity 48:911-22.
  3.  Maschalidi S et al, 2017. Nat Comm 21;8(1):1640.
  4. Nunes-Hasler P et al, 2017. Nat Comm 24;8(1):1852.
  5. Srikanth P et al, 2019. Nat Immunol 20:152-162.

Dernières Publications en lien avec le projet :

– Nunes-Hasler P, Maschaladi S, Lippens C, Castelbou C, l Bouvet S, Guido D, Bassoy ES, Page N, Merkler D, Hugues S, Martinvalet D, Manoury B, Demaurex N. STIM1 promotes migration, phagosomal maturation and antigen cross- presentation in dendritic cells. 2017 Nat Commun Nov 24;8(1):1852. doi: 10.1038/s41467-017-01600-6.

– Maschalidi S, Nunes-Hasler P, Nascimento C, Salent I, Lannoy V, Garfa-Traore M, Cagnard N, Sepulveda FE, Vargas P,  Lennon-Duménil AM, van-Endert P, Capiod T, Demaurex  N, Darasse-Jèze G, Manoury B. UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells. 2017 Nat Commun. Nov 21;8(1):1640. doi: 10.1038/s41467-017-01601-5.

– Babdor J, Descamps D, Adiko AC, Tohmé M, Maschalidi S, Evnouchidou I, Vasconcellos LR, De Luca M, Mauvais FX, Garfa-Traore M, Brinkmann MM, Chignard M, Manoury B*,  Saveanu L*. IRAP+ endosomes restrict TLR9 activation and signaling. 2017 Nat Immunol May;18(5):509-518doi: 10.1038/ni.3711. *Co-last and corresponding authors.

Ce projet s’inscrit-il dans la perspective d’une thèse :
oui X

ED d’appartenance : ED BioSPC

FicheaccueilM2-BMC-2021-2022 _BM

Equipes d’Accueil : 

Intitulé de l’Unité : Institut Necker Enfants Malades

Nom du Responsable de l’Unité : Fabiola Terzi
Nom du Responsable de l’Équipe : Bénédicte Manoury

Institut Necker Enfants Malades, 156-160 rue de sèvres 75015 Paris