Jonathan Coquet Project

Projects

1. Helper T cells : Generals of the immune response

The immune response has the challenge of responding to a broad variety of stimuli. From cancers to viruses, bacteria, worms and toxins, the type of response required to combat these threats differs. What may be a beneficial response in the context of a viral infection will not necessarily be effective to fight off bacteria. For this reason, the immune system needs to be flexible. One cell type in the immune system, known as the helper T cell is responsible for maintaining this flexibility. Helper T cells are known to differentiate into specialised subtypes with distinct functions and this divergence is controlled by various extracellular, intracellular and nuclear signals. My work focuses on characterising the involvement of helper T cells in diseases such as asthma and multiple sclerosis, and in finding novel pathways and proteins that regulate their differentiation.


Type 2 mediated inflammation in the airways leads to goblet cell metaplasia’ after the first point on ’t helper cells

2. The role of CD27-CD70 in chronic infection and cancer

Costimulatory pathways are critical regulators of immune homeostasis. Many chronic disorders are characterised by aberrant expression of costimulatory molecules. In particular, the TNF family member CD70 is expressed on malignant cells and in chronic viral infection and is proposed to  negatively impact on immune function. We will study the mechanism by which this pathway may impede immune function, hopefully paving the way to novel treatments for chronic diseases.

Selected Publications

PPAR-γ promotes type 2 immune responses in allergy and nematode infection
Ting Chen, Christopher A. Tibbitt, Xiaogang Feng,  Julian M. Stark, Leona Rohrbeck,  Lisa Rausch, Saikiran K Sedimbi, Mikael C. I. Karlsson, Bart N. Lambrecht, Gunilla B. Karlsson Hedestam, Rudi W. Hendriks, Benedict J. Chambers, Susanne Nylén and Jonathan M. Coquet
Science Immunology  10 Mar 2017: Vol. 2, Issue 9, DOI: 10.1126/sciimmunol.aal5196
Read the full text article here

lck-Driven Cre Expression Alters T Cell Development in the Thymus and the Frequencies and Functions of Peripheral T Cell Subsets
Carow B, Gao Y, Coquet J, Reilly M, Rottenberg ME.
J Immunol. 2016 Sep 15;197(6):2261-8. doi: 10.4049/jimmunol.1600827

Interleukin-21-Producing CD4(+) T Cells Promote Type 2 Immunity to House Dust Mites.
Coquet J, Schuijs M, Smyth M, Deswarte K, Beyaert R, Braun H, et al
Immunity 2015 Aug;43(2):318-30

The importance of co-stimulation in the orchestration of T helper cell differentiation.
Coquet J, Rausch L, Borst J
Immunol. Cell Biol. 2015 Oct;93(9):780-8

The CD27 and CD70 costimulatory pathway inhibits effector function of T helper 17 cells and attenuates associated autoimmunity.
Coquet J, Middendorp S, van der Horst G, Kind J, Veraar E, Xiao Y, et al
Immunity 2013 Jan;38(1):53-65

Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+ regulatory T cell development via the CD27-CD70 pathway.
Coquet J, Ribot J, Bąbała N, Middendorp S, van der Horst G, Xiao Y, et al
J. Exp. Med. 2013 Apr;210(4):715-28

IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism.
Zotos D, Coquet J, Zhang Y, Light A, D'Costa K, Kallies A, et al
J. Exp. Med. 2010 Feb;207(2):365-78

Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population.
Coquet J, Chakravarti S, Kyparissoudis K, McNab F, Pitt L, McKenzie B, et al
Proc. Natl. Acad. Sci. U.S.A. 2008 Aug;105(32):11287-92

Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis.
Coquet J, Chakravarti S, Smyth M, Godfrey D
J. Immunol. 2008 Jun;180(11):7097-101

Recruitment

We are always looking for enthusiastic researchers to join the group, so don’t be afraid to contact Jonathan Coquet on the email address below

Funding

Jonathan is supported by funding from the Swedish Research Council, Cancerfonden, KI foundations, Ollie and Elof Ericsson Stiftelse and Jeanssons stiftelse

Project members

Forskarassistent

Jonathan Coquet

Telefon: 08-524 869 52
Enhet: Gunilla Karlsson Hedestam grupp
E-post: jonathan.coquet@ki.se

Postdoc

Chris Tibbitt

Telefon: 08-524 869 46
Enhet: Gunilla Karlsson Hedestam grupp
E-post: chris.tibbitt@ki.se

Doktorand

Julian Stark

Telefon: 08-524 869 46
Enhet: Gunilla Karlsson Hedestam grupp
E-post: julian.stark@ki.se

Postdoc

Leona Rohrbeck

Enhet: Gunilla Karlsson Hedestam grupp
E-post: leona.rohrbeck@ki.se

Anknuten

Natalia Gonzalez Mancha

Enhet: Gunilla Karlsson Hedestam grupp
E-post: natalia.gonzalez.mancha@ki.se