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 previously 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 are performing 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 the progression of allergic diseases and ultimately help in the development of novel therapeutic approaches.
More recently, we have become interested in the study of the function of ILC2s in the bone marrow (BM). Classically, ILC2s in the BM were thought to serve as progenitors to give rise to ILC2s that will seed peripheral tissues. However, recent evidence showing a functional role for ILC2s in the BM is raising. We study how ILC2s influence bone marrow healthy and malignant hematopoiesis with a focus on bone marrow fibrosis.
Selected publications
Human CD127 negative ILC2s show immunological memory.
Mathä L, Krabbendam L, Martinez Høyer S, Heesters BA, Golebski K, Kradolfer C, Ghaedi M, Ma J, Stadhouders R, Bachert C, Cardell LO, Zhang N, Holtappels G, Reitsma S, Helgers LC, Geijtenbeek TBH, Coquet JM, Takei F, Spits H, Martinez-Gonzalez I
J Exp Med 2024 Aug;221(8):
New insights into ILC2 memory.
Martinez-Gonzalez I, Takei F
Immunol Rev 2024 May;323(1):118-125
Laboratory mice with a wild microbiota generate strong allergic immune responses.
Ma J, Urgard E, Runge S, Classon CH, Mathä L, Stark JM, Cheng L, Álvarez JA, von Zedtwitz S, Baleviciute A, Martinez Hoyer S, Li M, Gernand AM, Osbelt L, Bielecka AA, Lesker TR, Huang HJ, Vrtala S, Boon L, Beyaert R, Adner M, Martinez Gonzalez I, Strowig T, Du J, Nylén S, Rosshart SP, Coquet JM
Sci Immunol 2023 Sep;8(87):eadf7702
Tissue Resident and Migratory Group 2 Innate Lymphoid Cells.
Mathä L, Takei F, Martinez-Gonzalez I
Front Immunol 2022 ;13():877005
The Fate of Activated Group 2 Innate Lymphoid Cells.
Mathä L, Martinez-Gonzalez I, Steer CA, Takei F
Front Immunol 2021 ;12():671966
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
- KID funding (2025/2029)
- Cancerfonden (2023/2027)
- Wallenberg Academy Fellow (2020/2026)
- KI Assistant professor position (2020/2026)
- VR Starting grant (2019/2024)