Jonathan Coquet Group
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.
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.
The Metabolic Requirements of Th2 Cell Differentiation.
Stark JM, Tibbitt CA, Coquet JM
Front Immunol 2019 ;10():2318
Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells.
Tibbitt CA, Stark JM, Martens L, Ma J, Mold JE, Deswarte K, et al
Immunity 2019 07;51(1):169-184.e5
Multi-faceted inhibition of dendritic cell function by CD4Foxp3 regulatory T cells.
Seitz C, Liu S, Klocke K, Joly A, Czarnewski P, Tibbitt C, et al
J. Autoimmun. 2019 Mar;98():86-94
Atrophy of skin-draining lymph nodes predisposes for impaired immune responses to secondary infection in mice with chronic intestinal nematode infection.
Feng X, Classon C, Terán G, Yang Y, Li L, Chan S, et al
PLoS Pathog. 2018 05;14(5):e1007008
Factoring in CD4 T cells during treatment of HIV.
Immunol. Cell Biol. 2017 08;95(7):571-572
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 JM, Middendorp S, van der Horst G, Kind J, Veraar EA, 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 JM, Ribot JC, 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 JM, 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 JM, Chakravarti S, Kyparissoudis K, McNab FW, Pitt LA, McKenzie BS, 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 JM, Chakravarti S, Smyth MJ, Godfrey DI
J. Immunol. 2008 Jun;180(11):7097-101
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
Jonathan is supported by funding from the Swedish Research Council, Cancerfonden, KI foundations, Ollie and Elof Ericsson Stiftelse and Jeanssons stiftelse