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Tamara Sneperger

Research project: Deciphering the function(s) of the C-type lectin DCIR

C-type lectins (CLRs) form a superfamily of proteins that recognize a broad repertoire of ligands (in particular glycoconjugates) and regulate immune functions. Several CLRs possess intracellular signaling motifs, such as an immunoreceptor tyrosine-based inhibition (ITIM)-motif in their cytoplasmic tail. Upon ligand recognition, signaling through ITIM-containing lectins is thought to inhibit immune cell activation and participates to maintaining immune tolerance.

 

My phD research project focusses on a particular CLR named “Dendritic Cell ImmunoReceptor” (DCIR), which is expressed by several myeloid cell types, including dendritic cells (DCs), macrophages and neutrophils. DCIR belongs to the Dectin-2 family of CLRs but, unlike all other members of this family, DCIR contains an ITIM motif in its cytoplasmic tail. As such, DCIR is generally believed to mediate inhibitory signals in myeloid cells through recruiting the tyrosine phosphatases SHP-1 and SHP-2, which makes this CLR unique among the Dectin-2 family members.
Previously, DCIR has been shown to regulate the immune response in various pathological contexts including infection and autoimmunity. However, the DCIR ligands and signaling pathway remain poorly understood. Our laboratory has previously demonstrated that mDCIR1 (the closest murine homolog human DCIR, hDCIR) impairs anti-mycobacterial Th1 immune response through sustaining type I interferon (IFN)-mediated down-modulation of interleukin (IL)-12 in a SHP-2-dependent manner. Increased IL-12 production and Th1 activation in M. tuberculosis-infected mDCIR1-KO animals translated into reduced bacterial burden in the lungs but also into increased immunopathology. Surprisingly, we found that mDCIR1 does not recognize M. tuberculosis ligands, strongly suggesting that this receptor binds yet uncharacterized endogenous « danger » ligand(s), produced during inflammation. The central tenet of this project is to characterize both the ligand(s) and signaling pathway of DCIR to understand how DCIR impact the type-I IFN pathway in DCs, but also in macrophages, relevant not only in immunity to TB but in the greater context of a number of inflammatory diseases.

 

Curriculum vitae

Education

  • PhD (2018-), Immunology and infectious diseases, under the supervision of Drs. Yoann Rombouts and Olivier Neyrolles

Funding: Ministry of Higher Education & Research
Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse

  • Master degree (2016-2018), Immunology and infectious diseases

Université Toulouse III Paul Sabatier, Toulouse

  • Licence degree (2013-2016), Cellular biology and physiology

Université Toulouse III Paul Sabatier, Toulouse

 

Internships

  • 2018 (5 months): The role of the C-type lectin DCIR in the regulation of inflammasomes

Olivier Neyrolles’ laboratory, under the supervision of Yoann Rombouts
Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse

  • 2017 (2 months): Deciphering the signaling pathway of the C-type lectin DCIR

Olivier Neyrolles’ laboratory, under the supervision of Yoann Rombouts
Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse

  • 2016 (2 months): The evolution of the mouse metabolic phenotype in response to a high fat diet

Dominique Langin’s laboratory, under the supervision of Etienne Mouisel
Institut des Maladies Métaboliques et Cardiovasculaire (I2MC), Toulouse

  • 2015 (1 month): Structures and functions of molecular chaperones

Pierre Genevaux’s laboratory, under the supervision of Marie-Pierre Castanié-Cornet and Michèle Coddeville
Laboratoire de Microbiologie et Génétique Moléculaires (LMGM), Toulouse

 

Training

  • 2019: Animal experimentation « Utilisation et protection de l’animal de laboratoire, fonction concepteur et réalisateur des procédures expérimentales »

Ecole nationale vétérinaire de Toulouse (ENVT), Toulouse

  • 2019: BSL3 training

Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse

  • 2019: Training in biostatistics  

Université Toulouse III Paul Sabatier, Toulouse