Laboratory of Lymphocyte Differentiation – Jonathan Coquet Group

The Coquet and Martinez Gonzalez groups are focused on the study of T cell and Innate Lymphoid Cell (ILC) biology. We study activation, differentiation and memory formation primarily in the context of allergy and cancer. Identifying critical signals that induce the differentiation of T cells and ILC and their maintenance at tissue sites is our main interest. Strengths include preclinical models of infection, allergy and cancer as well as single cell RNA-Sequencing and flow cytometric analysis.

Research Description

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
An illustration
Illustration Jonathan Coquet group webpage


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.


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.

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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.

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Itziar Martinez Gonzalez Project

Immunological memory of Innate Lymphoid Cells

Our research interests are focused in the study of the biology of memory Group 2 Innate Lymphoid Cells (ILC2s) in type 2 immunity.

Research focus

ILC2s are innate lymphocytes involved in type 2 immune responses that protect us against parasites and play a role in tissue repair. However, they can also be pathogenic and induce allergic reactions. I described that ILC2s can become long-lived memory cells and mount more vigorous type 2 immune responses upon subsequent activation. The antigen non-specific nature of memory ILC2s has led me to hypothesize that these cells could be connecting unrelated allergic reactions as well as mediating allergen-independent exacerbations in allergic diseases.

We will perform an in-depth study of the transcriptome, proteome and epigenome of memory ILC2s in both mouse models of allergy and samples from allergic patients. We aim to understand how these innate lymphocytes contribute to allergic diseases and ultimately help in the development of novel therapeutic approaches.

Selected publications

Steroid-resistant human inflammatory ILC2s are marked by CD45RO and elevated in type 2 respiratory diseases.
van der Ploeg EK, Golebski K, van Nimwegen M, Fergusson JR, Heesters BA, Martinez-Gonzalez I, Kradolfer CMA, van Tol S, Scicluna BP, de Bruijn MJW, de Boer GM, Tramper-Stranders GA, Braunstahl GJ, van IJcken WFJ, Nagtegaal AP, van Drunen CM, Fokkens WJ, Huylebroeck D, Spits H, Hendriks RW, Stadhouders R, Bal SM
Sci Immunol 2021 Jan;6(55):

Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets.
Ghaedi M, Shen ZY, Orangi M, Martinez-Gonzalez I, Wei L, Lu X, Das A, Heravi-Moussavi A, Marra MA, Bhandoola A, Takei F
J Exp Med 2020 03;217(3):

ILC2 memory: Recollection of previous activation.
Martinez-Gonzalez I, Ghaedi M, Steer CA, Mathä L, Vivier E, Takei F
Immunol Rev 2018 05;283(1):41-53

ILC2 memory: Recollection of previous activation.
Martinez-Gonzalez I, Ghaedi M, Steer CA, Mathä L, Vivier E, Takei F
Immunol Rev 2018 05;283(1):41-53

Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients.
Sugita K, Steer CA, Martinez-Gonzalez I, Altunbulakli C, Morita H, Castro-Giner F, Kubo T, Wawrzyniak P, Rückert B, Sudo K, Nakae S, Matsumoto K, O'Mahony L, Akdis M, Takei F, Akdis CA
J Allergy Clin Immunol 2018 01;141(1):300-310.e11

Group 2 innate lymphoid cell activation in the neonatal lung drives type 2 immunity and allergen sensitization.
Steer CA, Martinez-Gonzalez I, Ghaedi M, Allinger P, Mathä L, Takei F
J Allergy Clin Immunol 2017 08;140(2):593-595.e3

Allergen-Experienced Group 2 Innate Lymphoid Cells Acquire Memory-like Properties and Enhance Allergic Lung Inflammation.
Martinez-Gonzalez I, Mathä L, Steer CA, Ghaedi M, Poon GF, Takei F
Immunity 2016 07;45(1):198-208

Common-Lymphoid-Progenitor-Independent Pathways of Innate and T Lymphocyte Development.
Ghaedi M, Steer CA, Martinez-Gonzalez I, Halim TYF, Abraham N, Takei F
Cell Rep 2016 Apr;15(3):471-480

Lung ILC2s link innate and adaptive responses in allergic inflammation.
Martinez-Gonzalez I, Steer CA, Takei F
Trends Immunol 2015 Mar;36(3):189-95

Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation.
Halim TY, Steer CA, Mathä L, Gold MJ, Martinez-Gonzalez I, McNagny KM, McKenzie AN, Takei F
Immunity 2014 Mar;40(3):425-35

Funding sources

  • VR Starting grant
  • Wallenberg Academy Fellow
  • KI Assistant professor position
  • Jeansson Stilftese
  • Sanofi Type 2 Innovation Grant

Group members

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Itziar Martinez Gonzalez

Assistant professor
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Sergio Martinez Hoyer

Postdoctoral researcher
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Laura Mathä

Postdoctoral researcher

Sergio Martinez Hoyer Project

My research aims to understand the cellular and molecular mechanisms underlying the biology and response to therapy in bone marrow diseases, with a focus on myeloid malignancies.

Currently, we are working on two projects:

  1. Role of innate lymphoid cells in bone marrow fibrosis. Specific genetic alterations in the hematopoietic stem cell compartment can lead to the development of scar tissue in the bone marrow, which then loses its ability to support normal hematopoiesis. Previous work has demonstrated a role for innate lymphocytes in the development of fibrosis in different organs. I am exploring the contribution of innate lymphoid cells to the formation of fibrotic tissue in a mouse model of bone marrow fibrosis.
  2. Identification of novel therapeutic targets in drug resistant myelodysplastic syndromes. My previous work on resistant MDS described the molecular mechanisms by which malignant cells escape the activity of lenalidomide in the bone marrow. Proof of principle experiments revealed that it should be possible to overcome drug resistance in mutated cells. Using a functional genomics approach on cell lines and primary tissue, we aim to identify novel therapeutic targets that effectively eliminate relapsed malignant cells.


Recent publications

A clinical transcriptome approach to patient stratification and therapy selection in acute myeloid leukemia.
Docking TR, Parker JDK, Jädersten M, Duns G, Chang L, Jiang J, Pilsworth JA, Swanson LA, Chan SK, Chiu R, Nip KM, Mar S, Mo A, Wang X, Martinez-Høyer S, Stubbins RJ, Mungall KL, Mungall AJ, Moore RA, Jones SJM, Birol İ, Marra MA, Hogge D, Karsan A.
Nat Commun. 2021 Apr 30;12(1):2474. 
Mechanisms of lenalidomide sensitivity and resistance.
Martinez-Høyer S, Karsan A.
Exp Hematol. 2020 Nov;91:22-31. 

Loss of lenalidomide-induced megakaryocytic differentiation leads to therapy resistance in del(5q) myelodysplastic syndrome.
Martinez-Høyer S, Deng Y, Parker J, Jiang J, Mo A, Docking TR, Gharaee N, Li J, Umlandt P, Fuller M, Jädersten M, Kulasekararaj A, Malcovati L, List AF, Hellström-Lindberg E, Platzbecker U, Karsan A.
Nat Cell Biol. 2020 May;22(5):526-533. 



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Sergio Martinez Hoyer

Research Specialist