Jonathan Coquet Group
Our group is interested in how T cells develop and differentiate in response to antigens and cytokines. In particular, the group is focused on understanding the role of T cells in allergy and cancer.
T cells recognise peptide/lipid ligands presented in the context of MHC or MHC-like molecules expressed on antigen presenting cells. In particular, the group has a special focus on CD4 T cells, which when activated differentiate into T helper cells with potent cytokine-secreting function. Over the past three decades, several distinct T helper cell subsets have been described including Th1, Th2, Th17, Treg and others and these all exert quite unique immune modulatory effects. My group has many interests, including:
- Understanding how T helper cells promote health and disease
- Deciphering factors that regulate T helper cell function and differentiation
- Phenotyping T helper cells in lymphoid and non-lymphoid tissues in diseased and healthy contexts
- Probing for other functionalities in the T helper cell spectrum
- Understanding how environmental factors may impact on T helper cell functions
Our group is interested in understanding immune responses to allergens. T helper cells, in particular IL-4, IL-5 and IL-13 producing Th2 cells have a central role in mediating the pathogenesis of asthma. Over the last few years, we have demonstrated that these cells are characterised by the high expression of genes associated with lipid metabolism including PPAR-g, which likely regulates metabolism in Th2 cells and also promotes effector gene expression.
Many other T helper cell subsets are thought to regulate asthma, especially in adults, and we are interested in characterising T helper cells in different phenotypes of asthma and allergy. Right now, we have a focus on performing single cell RNA-Sequencing analyses in different clinical and preclinical contexts, in order to paint a really clear picture of the T helper cell phenotype in different allergies.
An important factor in the striking rise in allergy incidence over the last few decades has been a complete upheaval in our way of life. Our infectious landscape, diets, living conditions and many other things have changed dramatically over this time, and many of these factors are associated with a rise in the incidence of allergies. We are now devoting more time into understanding how some of these factors from our environment may be affecting allergic sensitisation and aiming to model these in our preclinical allergy models.
There is an increasing appreciation that the immune system is intricately involved in the process of cancer initiation and growth. The bulk of research into cancer immunology has focussed on the role of CD8 T cells, and for good reason. However, understanding the role of CD4 T cells and harnessing their full potential is likely to lead to even better outcomes for patients with cancer. Our group is actively pursuing the elucidation of novel genes that may regulate the function of CD8 T lymphocytes in cancer. Further, we are interested in understanding more fully what impact CD4 T cells may have on the process of cancer development, and how these cells may be harnessed to potentiate cancer immunotherapy.
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 and has been supported by funding from the Swedish Research Council, Cancerfonden, Barncancerfonden, KI foundations, Ollie and Elof Ericsson Stiftelse, Klas Groschinsky foundation and Sagens Stiftelse.