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Biologie Cellulaire - Endothelial cells in Immunity, Inflammation and Cancer

Jean-Philippe Girard

Responsable groupe

FR - Our team is among the world leaders for the characterization of high endothelial venules (HEVs), portals of entry for lymphocytes into lymphoid organs, inflamed and tumor tissues (~ 25 years expertise), and for the study of IL-33, a nuclear cytokine from the IL-1 family that we discovered in 2003, which plays crucial roles in innate immunity and allergic inflammation.

 

eq_girard.jpgWe demonstrated that dendritic cells, which are well known for their role as antigen-presenting cells, play an unexpected and important role in the maintenance of HEV blood vessels in lymph nodes (Nature 2011).

In addition, we discovered the frequent presence of HEVs in human solid tumors, and their association with cytotoxic lymphocyte infiltration and favourable clinical outcome in breast cancer.

FRançais 

 

 

Our study introduced a novel concept in cancer biology “Blood vessels in human tumors are not all the same and some types of blood vessels found in the tumor microenvironment (i. e. HEVs) can contribute to tumor suppression rather than tumor growth” (Cancer Res 2011).

A better understanding of HEVs at the molecular level, which is one of the major objectives of our team, may have an important impact for cancer therapy.

Our team showed that IL-33 is a chromatin-associated cytokine (PNAS 2007, 543 citations) that function as an alarm signal (alarmin) released upon cellular damage (PNAS 2009, 373 citations>).

We demonstrated that inflammatory proteases can generate truncated forms of IL-33 that are 30-fold more potent than the full length protein for activation of group 2 innate lymphoid cells (PNAS 2012, 193 citations, PNAS 2014).

 

Recently, we discovered that full length IL-33 functions as a protease sensor that detects proteolytic activities associated with a large variety of environmental allergens (Nature Immunology 2018). An important objective of our team is to further characterize IL-33 regulation and mechanisms of action in vivo, through the use of multidisciplinary approaches.

 

Our research topics

Main publications - FR

  • Cayrol C et al. (2018) Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33. Nature Immunology 19: 375-385
  • Liew FY, Girard JP and Turnquist HR (2016) Interleukin-33 in health and disease. Nature Rev Immunol 16: 676–689
  • Girard JP, Moussion C and Forster R. (2012) HEVs, Lymphatics and homeostatic immune cell trafficking in lymph nodes. Nature Rev Immunol 12: 762-773
  • Martinet L et al. (2011) Human solid tumors contain high endothelial venules (HEV): association with T and B lymphocyte infiltration and favourable prognosis in breast cancer. Cancer Res 71: 5678-5687
  • Moussion C and Girard JP. (2011) Dendritic cells control lymphocyte entry to lymph nodes via high endothelial venules. Nature 479: 542-546

 

image_girard_science.jpgHigh endothelial cells from HEVs (green) are characterized by a plump morphology and express high levels of the nuclear cytokine IL-33 (red).

 

Scientists

Jean-Philippe Girard

INSERM Research director

Emma Lefrançais

CNRS Research associate in immunology

Nathalie Ortéga

Associate Professor in Molecular Biology - University of Toulouse

Assistants de recheche

Elisabeth Bellard

CNRS Engineer

Stéphane Roga

Pauline Schmitt

CNRS Engineer

Etudiantes

Lucas Blanchard

Fellow of the 'Fondation pour la recherche médicale'

Juliette Coudert

Fellow of the Ministry of Higher Education & Research

Robin Laffont

Fellow of the Ministry of Higher Education & Research