Elucidating the role of secretory leukocyte protease inhibitor in Sjögren syndrome.

The Research Project:
Sjögren’s syndrome (SjS) is a chronic autoimmune disease characterized by the destruction of exocrine glands by self-reactive immune cells. About 0.5% of the population is affected with dry mouth and eyes and there is no cure against the disease. The immunopathology of SjS is complex and associated with an intricate crosstalk between various cell types including salivary gland epithelial cells (SGECs), lymphocytes, and innate immune cells. Recent research in the field of autoimmunity, revealed the critical role of antimicrobial peptides (AMPs) in preventing these diseases via their strong immunoregulatory capacity. Among them the secretory leukocyte protease inhibitor (SLPI) is highly expressed by the SGECs and systemic SLPI levels are elevated in patients with SjS. SLPI present in the extracellular milieu can penetrate neighboring cells and modulate the function of various immune cells. Our objective is therefore to determine the role of SLPI in the exocrine glands during the development of SjS in murine models and using patient samples. Our project will provide new perspectives in the
immunopathology of SjS and could offer new therapeutic opportunities.

Research keywords: Antimicrobial peptides, autoimmunity, mouse models, gut microbiota.

The Applicant:
The applicant should be a highly motivated postdoctoral candidate with a PhD degree in Immunology and a high-quality track record. He/she should have a strong background in performing research in mouse immunology.

The Research Environment:
The research Unit is Institut Necker Enfants Malades (INEM), a biomedical research center aiming at fundamental discoveries with the potential of leading to therapeutic progress, focusing on incurable chronic diseases. Our faculty includes 19 teams with an international background and two departments:
« Cell Biology (growth and signaling) » and « Immunology, Infectiology, and Hematology ». INEM shares a unique research campus with the IMAGINE institute and the Hôpital Necker-Enfants Malades, which, supported by state-of-the-art core facilities, together provide a rich and vibrant environment for basic research and translational innovation. PIs at INEM have first-rate expertise in immunology, basic physiology, cellular biology, and molecular biology. The INEM teams collaboratively address multiple facets of diseases.

Julien Diana, PhD
Institut Necker Enfants Malades
160, rue de Vaugirard
75015 Paris, FRANCE
E-mail :[email protected]

To apply:
The candidate should send a curriculum with a brief statement of research experience, technical expertise, and interests, and one or two references to Julien Diana.

Postdoc fellowship:
24 months. Net salary 2200 €/month from the Inserm. Starting in January 2023.

Selected references from the PI:
-NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner. Diana J, Griseri T, Lagaye S, Beaudoin L, Autrusseau E, Gautron AS, Tomkiewicz C, Herbelin A, Barouki R, von Herrath M, Dalod M, Lehuen A. Immunity 2009. (IF :24.2).

-Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay. Diana J, Brezar V, Beaudoin L, Dalod M, Mellor A, Tafuri A, von Herrath M, Boitard C, Mallone R, and Lehuen A. J. Exp. Med. 2011. (IF :15.1).

-Crosstalk between neutrophils, B-1a cells and plasmacytoid dendritic cells initiates autoimmune diabetes. Diana J*, Simoni Y, Furio L, Beaudoin L, Agerberth B, Barrat F, and Lehuen A. Nat. Med. 2013. (IF :22.5) (*: corresponding author).

-Macrophages and β-cells are responsible for CXCR2-mediated neutrophil infiltration of the pancreas during autoimmune diabetes. Diana J* and Lehuen A. EMBO Mol. Med. 2014; (IF:9.4); (*: corresponding author).

-Pancreatic β-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota. Sun J, Furio L, Mecheri R, van der Does A, Lundeberg E, Saveanu L, Chen Y, van Endert P, Agerberth B, and Diana J. Immunity 2015. (IF: 21.5).

-Lactose Induces Phenotypic and Functional Changes of Neutrophils and Macrophages to Alleviate Acute Pancreatitis in Mice. Li-Long Pan, Yuan-Yuan Deng, Chengfei Wu, Jiahong Li, Wenying Niu, Madhav Bhatia, Birgitta Agerberth, Gudmundur H. Gudmundsson, Julien Diana†, Jia Sun†. Front. Immunol. 2018.
(IF: 6.4). (†: authors contribute equally).

-Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes. Miani M, Le Naour J, Enée E, Verma SC, Straube M, Emond P, Ryffel B, van Endert P, Sokol H, Diana J. Cell Metab. 2018. (IF: 20.5).

-The Dual Role of Antimicrobial Peptides in Autoimmunity. Liang W, Diana J. Front Immunol. 2020. (IF:4.5).

-Gut microbiota-CRAMP axis shapes intestinal barrier function and immune responses in dietary gluten-induced enteropathy. Ren Z, Pan LL, Huang Y, Chen H, Liu Y, Liu H, Tu X, Liu Y, Li B, Dong X, Pan X, Li H, Fu YV, Agerberth B, Diana J†, Sun J†. EMBO Mol. Med. 2021 (IF:10.2) (†: authors contribute equally).

-Intestinal Cathelicidin Antimicrobial Peptide Shapes a Protective Neonatal Gut Microbiota against Pancreatic Autoimmunity. Liang W, Enée E, Andre-Vallee C, Falcone M, Sun J, Diana J. Gastroenterology 2022 (IF:22.6).