PhD Scientific Days 2023

Translational Medicine - Posters P

Role of Sirpa in Post-Septic Pulmonary Immunity

Előadó neve

CHAHWAN, Valeria, PhD

Neptun code

0

Előadó munkahelye

Nantes Université

Előadó telefonszáma

+33695759615

Előadó e-mail címe

valeriachahwane@hotmail.com

Az előadás címe

Role of Sirpa in Post-Septic Pulmonary Immunity

Szerző(k) neve és munkahelye

1 Nantes Université, Inserm, Center for Research in Transplantation and Translational Immunology,
UMR1064, Nantes, France
2 Surgical intensive care unit,CHU Nantes, Franc

Bemutatás módja

Poszter

Szekció

Translational Medicine - Posters P

Language of the presentation

English

Preferred session

Health Sciences

Összefoglaló szövege

Patients hospitalized with sepsis or trauma have a higher risk of developing hospital-acquired pneumonia (HAP) due to an immune suppressive effect of the condition that led to hospitalization. To date, the only available treatments for HAP are antibiotics, which aim to prevent lung contamination and maintain sterile airways, but the attributable mortality remains higher than 10%. We are now developing a new concept that has the potential to overcome the classical theory of pneumonia genesis and revolutionize the prevention and treatment of this condition.
Alveolar macrophages (R-MAC) provide the first line of defense against respiratory pathogens. After the resolution of inflammation, we reported on a long-lasting inability of R-MAC to effectively phagocytose bacteria. We showed that R-MAC underwent an epigenetic program of tolerogenic training that led to their ‘immunoparalysis’. We found that the changes in the microenvironment observed during pneumonia are in part mediated by the stimulation of the Sirpa receptor, resulting in the reduced phagocytic capacity of the R-MAC.
We hypothesize that Sirpa signaling early after the primary inflammation triggers an immune-suppressive lung environment, leading to functional impairment of R-MAC.
We are now investigating (1) the chemical blockade of Sirpa by targeting both allosteric and catalytic sites of SHP2 (downstream molecule of the Sirpa pathway) aiming to restore the phagocytic capacity of R-MACs and (2) the signaling pathway by which Sirpa modifies the microenvironment.
We are associating
1. in silico transcriptomic analysis (scRNAseq, RNAseq and ATAC-seq),
2. in vivo analysis on our model of Sirpa knockout mouse (Sirpa-/-) by flow cytometry,
3. and in vitro culture of bone-marrow derived macrophages (BMDMs) from Sirpa+/+ and Sirpa-/- mice
to be able to identify Sirpa-dependent functions that induce an immunosuppressive lung environment in patients.
The in vitro model of Sirpa stimulation on BMDMs by the surfactant protein D is allowing to investigate the signaling pathway of Sirpa. Transcriptomic analysis revealed the agonists of the microenvironment interacting with Sirpa in the time of inflammation. Plus, preliminary results with chemistry-driven optimization of SHP2 inhibitors is increasing the phagocytic capacity of murine macrophages, suggesting a promising strategy for human patients with pneumonia.

University and Doctoral School

Other, please specify in the next box

Other university and doctoral school, not listed above

Nantes Université, Biology and Health doctoral school

Supervisor

Pr ROQUILLY Antoine

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7457

Start

11:24

End

11:29

Authors (legacy)

1 Nantes Université, Inserm, Center for Research in Transplantation and Translational Immunology,
UMR1064, Nantes, France
2 Surgical intensive care unit,CHU Nantes, Franc