Jenny Mjösberg group - Innate lymphoid cells (ILCs)

The purpose of the research conducted in the Jenny Mjösberg group is to characterize the role for innate lymphoid cells (ILCs) in intestinal inflammation and cancer. The aim of our research is ultimately to increase the understanding of disease mechanisms, discovering novel treatment targets and strategies for patient stratification in biologics treatment.

Jenny Mjösberg Research group
Jenny Mjösberg Research group Photo: Private

Innate lymphoid cells (ILCs) serve as first-line tissue sentinels, integrating stromal- and immune-cell derived signals to monitor homeostasis, respond to infections and contribute to tissue repair at barrier surfaces such as the lung and gut. More and more data indicate that they might also be involved in disease, such as inflammatory bowel disease (IBD) and cancer in the gut, as well as inflammation in the airways (asthma). We are trying to gain insight into basic ILC biology; how these cells are differentiated, regulated and interact with other cells in the immune system. We perform these studies in the context of gut and lung inflammation and gut cancer with the ultimate aim of increasing the understanding of disease mechanisms, discovering novel treatment targets and strategies for patient stratification in biologics treatment.

Our research is set up in a truly translational fashion, where we address complex immunological questions in unique tissue material from patients with inflammation or tumors. For this, we use advanced single-cell based techniques such as flow cytometric analysis and sorting, in vitro cell assays as well as several molecular techniques including single-cell RNA-sequencing and ATAC-seq.

Group Leader

Jenny Mjösberg

PhD, Associate Professor

During her postdoc period in the laboratory of Hergen Spits at the AMC in Amsterdam, she contributed to a new field in immunology with the identification of two novel subsets of human innate lymphoid cells (ILC1 and ILC2). The Mjösberg group is now focused on the importance of human ILCs in mucosal homeostasis and inflammation, mainly the lung and gastrointestinal tract. Importantly, her group provided the first transcriptional characterization of human ILCs on the single-cell level.

Group members

Chris Tibbitt

Researcher

Chris completed his PhD studies at Newcastle University in 2015 characterizing the influence of TCR signaling on the development of autoimmune Th17 cells. Since joining the Mjösberg group in Feb 2020 his focus has been on understanding ILC heterogeneity across intestinal compartments through the application of single cell technologies.

Anna Carrasco

PhD, postdoc

Anna completed her PhD in the University of Barcelona in 2016, studying in the immune profile in celiac disease and inflammatory bowel disease. She joined the Mjösberg group in June 2017 as a Postdoc and is now focusing on ILC compartmentalization throughout the human gut immune niches.

Anne Marchalot

PharmD, Postdoc

I did my industrial pharmacy studies and got a master's degree in cellular and molecular infectiology, vaccinology and therapeutic antibodies from Tours University. Then, I joined a research team in Limoges University where I worked one year as a research engineer and did my PhD studies specializing in antisense oligonucleotide based gene therapy in B cell and plasma cell in Limoges University.

Chris Stamper

PhD, Postdoc

Chris completed his doctoral studies in Immunology at the University of Chicago in May 2021. His studies focused on how the evolutionary history of the B cell receptor impacts somatic hypermutation and using single cell sequencing and monoclonal antibody techniques to characterize human B cell and antibody responses to an experimental universal influenza vaccine and SARS-CoV-2 infection. In the Mjösberg lab he will use similar single cell approaches to characterize intestinal lymphocytes.

Ram Vinay Pandey

Bioinformatician

Efthymia Kokkinou

MSc., PhD student

She completed her Bachelor's Degree in Greece in 2014 and her Master's Degree at Stockholm University and Karolinska Institute in 2016. In her Master's thesis she addressed the characterization and development of regulatory T-cells (Tregs) in premature infants supplemented with probiotics. She joined Jenny Mjösberg's group in June 2016 as a Research Assistant to work on the role of Innate Lymphoid Cells (ILCs) in human colorectal cancer. In May 2017 she started her PhD focused on the regulation of human ILC plasticity in adult and paediatric Inflammatory Bowel Disease.

Lorenz Wirth

MSc., PhD student

Lorenz studied medical biotechnology at the Technical University of Berlin where he worked on the characterization of a 3d model of the human hematopoietic stem cell niche during his Bachelor’s thesis. He completed his Master’s thesis at the German Rheumatism Research Center in Berlin, focusing on the selective expression and regulation of a specific gene in T helper cell subsets. In May 2020 he joined Jenny Mjösberg’s group for his PhD, studying ILC plasticity in the context of eicosanoid expression and regulation. This project is part a collaboration with AstraZeneca Gothenburg and is performed within the European funded INITIATE training network.

Luca Mazzurana

PhD

He received his Bachelor of Science from the University of Hawaii in 2013 and his master degree from Stockholm University in 2015, where he worked on the functional characterization of a Crohn’s disease associated gene. He joined the group in November 2015 as a PhD student, focusing on the heterogeneity and role of innate lymphoid cells in inflammatory bowel disease

Whitney Weigel

PhD, Lab manager

Whitney completed her doctoral work at the University of Louisville in 2015 where she worked on the impact of catecholamine hormones on bacteria causing periodontal disease. From 2016-2018, she worked as a postdoctoral fellow at the Helmholtz Center for Infection Research studying the virulence mechanisms of Yersinia pseudotuberculosis. She also a completed a postdoctoral fellowship at the University of Ottawa from 2018-2020 that used organoids as a model for inflammatory bowel disease. From 2020 she has been working as a lab manager in the lab of Jenny Mjosberg at the Karolinska Institute.

Former group members

  • Tea Soini, postdoc
  • Anna Rao, postdoc
  • Isabel Meininger, postdoc
  • Aline Van Acker, postdoc
  • Viktoria Konya, PhD, postdoc
  • Lena Berglin, PhD, postdoc
  • Marianne Forkel, PhD student
  • Jovana Maric, visiting PhD student
  • Avinash Ravindran, PhD student

Collaborations

In addition to several collaborations within the Center for Infectious Medicine, we currently collaborate with the following researchers and clinicians:

  • Caroline Nordenvall, Ulrik Lindforss, Gabriella Jansson-Palmer; Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
  • Charlotte Höög and Charlotte Hedin, Division of Gastroenterology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  • Peter Thelin Schmidt, Juan Arkani, Department of Medicine Solna, Karolinska Institutet and Department of Medicine, Ersta Hospital, Stockholm, Sweden
  • Fredrik Linder, Stockholm Gastrocenter, Stockholm, Sweden
  • Helena Rolandsdotter, Erik Melén, CLINTEC, Södersjukhuset, Karolinska Institutet and Sachs' Children and Youth Hospital, Stockholm, Sweden
  • Sven-Erik Dahlén, Jesper Säfholm, Johan Kolmert. Experimental Asthma and Allergy Research Unit, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  • Craig Wheelock, Division of Physiological Chemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
  • Apostolos Bossios, Center for Allergy Research, Karolinska Institutet; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Huddinge and Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
  • Mattias Jangard, ENT Unit, Research Laboratory, Sophiahemmet University, Stockholm, Sweden
  • Danielle Friberg, Department of Otorhinolaryngology, Institute of Surgical Science, Uppsala University, Uppsala, Sweden
  • Thomas Höchdörfer, AstraZeneca
  • Carl Jorns, Department of Transplantation Surgery, Karolinska University Hospital Huddinge, CLINTEC, Karolinska Institutet, Stockholm, Sweden
  • Fabio Luciani, School of Medical Sciences and The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
  • David Withers, Institute of Immunology and Immunotherapy (III), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  • Hergen Spits, Department of Experimental Immunology, UMC, University of Amsterdam, Amsterdam, The Netherlands

Projects

Single-cell analysis of intestinal lymphocytes reveals targets for treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) constitutes an increasing global health burden, yet effective treatments are lacking. Here we use single-cell RNA-sequencing and functional assays to dissect the human intestinal lymphocyte compartments in IBD. With this approach, we will determine parallels between known and novel subsets of tissue-resident, inflammation-associated, innate and adaptive lymphocytes to reveal therapy targets. Building on this characterization, we will perform longitudinal assessments of intestinal lymphocytes from IBD patients on biological treatments to unveil immunological signatures of treatment response and unfold critical disease mechanisms.

Single-cell proteomics and transcriptomics characterization of innate and adaptive lymphocytes in colorectal cancer and peritoneal carcinomatosis

Every year about 6000 Swedes are diagnosed with colorectal cancer (CRC) of which around 30% develop peritoneal carcinomatosis (PC). We have previously reported disturbances in the composition of ILCs in IBD and CRC. However, the role of intratumoral ILCs and the functional parallels between ILCs and T cells in PC is unknown. To this end we are performing multidimensional single-cell analysis of proteins and transcripts in ILCs and T cells to reveal the characteristics, heterogeneity and functional parallels between ILCs and T cells which will advance our understanding of anti-tumor immunity.

Tissue-specific regulation of human ILC2 in allergy and asthma

Asthma affects over 300 million people globally and causes approximately 150 deaths in Sweden every year. We recently demonstrated a rapid accumulation of activated innate lymphoid cells type 2 (ILC2) in bronchioalveolar fluid following allergen-provocation in humans. The overall aim of this project is to determine the role for ILC2 in asthma with particular focus on how the microenvironment regulates ILC2 function and plasticity and the effect of novel biological treatments on ILC2.

Defining the metabolic signatures of tissue- and tumor-resident ILCs

Induction of any immune response requires metabolic changes. While a number of genes and pathways have been evaluated in T cells, the factors that link activation to alterations in metabolic state remains to be profiled in depth for human ILCs. Using the latest techniques in metabolic profiling and single cell mutli-omics we aim to map the metabolic profiles of human ILCs across a range of tissues and inflammatory conditions and assess whether biological therapies can impact upon cell intrinsic metabolism. We are also seeking to determine how host metabolic state (e.g. obesity) can alter the ILC phenotypes during asthma. PI: Chris Tibbitt.

Research support

  • European Research Council (ERC)

  • Swedish Foundation for Strategic Research (SSF)

  • Swedish Cancer Society

  • Swedish Research Council (VR)

  • Knut and Alice Wallenberg Foundation

  • Swedish Society for Medical Research (SSMF)

  • Karolinska Institutet

  • Erling-Persson Family Foundation

Publications

  1. Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing.
    Mazzurana L, Czarnewski P, Jonsson V, Wigge L, Ringnér M, Williams TC, Ravindran A, Björklund ÅK, Säfholm J, Nilsson G, Dahlén SE, Orre AC, Al-Ameri M, Höög C, Hedin C, Szczegielniak S, Almer S, Mjösberg J. Cell Res. 2021 Jan 8. doi: 10.1038/s41422-020-00445-x.
     
  2. Cytokines regulate the antigen-presenting characteristics of human circulating and tissue-resident intestinal ILCs.
    Rao A, Strauss O, Kokkinou E, Bruchard M, Tripathi KP, Schlums H, Carrasco A, Mazzurana L, Konya V, Villablanca EJ, Björkström NK, Lindforss U, Spits H, Mjösberg J.Nat Commun. 2020 Apr 27;11(1):2049.
     
  3. Cytokine-induced endogenous production of PGD2 is essential for human ILC2 activation.
    Maric J, Ravindran A, Mazzurana L, Björklund ÅK, van Acker A, Rao A, Kokkinou E, Ekoff M, Thomas D, Fauland A, Nilsson G, Wheelock CE, Dahlén E, Ferreirós N, Geisslinger G, Friberg D, Heinemann A, Konya V and Mjösberg J. J Allergy Clin Immunol (JACI). 2019 Jun; 143(6):2202-2214.
     
  4. Distinct alterations in the composition of mucosal innate lymphoid cells in newly diagnosed and established Crohn’s disease and ulcerative colitis.
    Forkel M, van Tol S, Höög C, Michaelsson J, Almer S and Mjösberg J. J Crohn’s and Colitis. 2019 Jan 1;13(1):67-78.
     
  5. Vitamin D downregulates the IL-23 receptor pathway in human mucosal ILC3
    Konya V, Czarnewski P, Rao A, Forkel M, Villablanca E, Almer S, Lindforss U, Friberg D, Höög C, Bergman P and Mjösberg J. . J Allergy Clin Immunol (JACI). 2018 Jan; 141(1):279-292.
     
  6. PGE2 suppresses human group 2 innate lymphoid cell function
    Maric J, Ravindran A, Mazzurana L, Björklund ÅK, van Acker A, Rao A, Friberg D, Dahlén E, Heinemann A, Konya V and Mjösberg J. . J Allergy Clin Immunol (JACI). 2018 May; 141(5):1761-1773.
     
  7. The heterogeneity of human CD127+ innate lymphoid cells revealed by single-cell RNA-sequencing.
    Björklund ÅK, Forkel M, Picelli S, Konya V, Theorell J, Friberg D, Sandberg R, Mjösberg J. Nat Immunol. 2016. 17(4):451-60. 
     
  8. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues.
    Bernink J, Peters C, Munneke M, te Velde A, Meijer S, Weijer K, Hreggvidsdottir H, Heinsbroek S, Legrand N, Buskens C, Bemelman W, Mjösberg J and Spits H. Nat Immunol. 2013; 14:221-9.
     
  9. Mjösberg J, Bernink J, Golebski K, Karrich JJ, Peters CP, Blom B, Te Velde AA, Fokkens WJ, van Drunen CM, Spits H. The Transcription Factor GATA3 Is Essential for the Function of Human Type 2 Innate Lymphoid Cells. Immunity. 2012; 19;37(4):649-59.
     
  10. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161
    Mjösberg J, M, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, Fokkens WJ, Cupedo T, Spits H. Nat Immunol. 2011; 11;12(11):1055-62.

All publications from Mjösberg group

Google Scholar