Human innate lymphoid cell lab – Jenny Mjösberg group

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

Part of the:
Group photo.

Our research

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 perform internationally leading clinical and translational lung and allergy research in the Clinical Lung and Allergy Research Unit (CLARU).

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.

Translational research

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.

In a video from Stiftelsen för strategisk forskning, SSF (in Swedish) Jenny Mjösberg explains the research conducted in the group. 
 

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, KI, 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.
  • Helena Rolandsdotter, Erik Melén; CLINTEC, Södersjukhuset, KI and Sachs' Children and Youth Hospital, Stockholm, Sweden.
  • Jesper Säfholm; Experimental Asthma and Allergy Research Unit, Institute of Environmental Medicine, KI, Stockholm, Sweden.
  • Craig Wheelock and Johan Kolmert; Integrative Metabolics. Institute of Environmental Medicine, KI, Stockholm, Sweden.
  • Apostolos Bossios; Lung and Airway research, Institute of Environmental Medicine, KI Stockholm, Sweden.
  • Mattias Jangard; ENT Unit, Research Laboratory, Sophiahemmet University, Stockholm, Sweden.
  • Thomas Höchdörfer, AstraZeneca.
  • Carl Jorns; Department of Transplantation Surgery, Karolinska University Hospital Huddinge, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
  • Matthew Hepworth; Division of Infection, Immunity & Respiratory Medicine (L5), Division of Immunology, Immunity to Infection and Respiratory Medicine, The University of Manchester.

Publications

Selected publications

All publications Jenny Mjösberg group:

PubMed

Publications on Google Scholar:

Google Scholar

Funding

Grants

  • Swedish Research Council
    1 January 2025 - 31 December 2029
    Biologics targeting type 2 cytokines offer new hope for patients with severe asthma, but not all patients respond, and none are cured. This calls for increased understanding of airway tissue type 2 lymphocytes and how they are regulated by biologics. Innate lymphoid cells type 2 (ILC2) and type 2 T cells (Th2 and Tc2), orchestrate type 2 inflammation. I will build on our unexpected finding that treatment with anti-interleukin (IL)-5 biologics causes an increase in circulating type 2 lymphocytes, implying biologics effects on lymphocyte trafficking, differentiation, and tissue residency. To test this hypothesis, I will capitalize on leading a clinical asthma research unit and immunology lab, enabling us to perform pioneering immunological studies using unique airway tissue samples from patients with severe asthma before and during biologics treatment. My translational team of clinical, immunological and computational researchers will determine the unique features of airway resident lymphocytes and the epigenetic and transcriptional effects of biologics on circulating and airway-resident lymphocytes. We will also dissect the mechanisms involved in lymphocyte trafficking and differentiation in the airways. This will increase the understanding of human airway lymphocyte diversification, trafficking, tissue residency and differentiation in relation to biologics treatment efficacy. Our studies will reveal new targets for treatment and means to better tailor the use of biologics.
  • Swedish Cancer Society
    1 January 2023
    Inflammatory bowel disease (IBD) means an increased risk of developing colorectal cancer, which is thought to be caused by intestinal inflammation giving rise to cell changes and cancer. However, what role the intestinal immune system, mainly lymphocytes such as T cells and innate lymphocytes (ILCs), which I recently discovered in humans, play in this process is unclear. We intend to answer this question by collaborating with clinical researchers where we can perform advanced immunological analyzes of intestinal samples from patients with IBD and colorectal cancer, before and after therapy. We intend to study intestinal lymphocytes with single-cell techniques at both gene expression and protein level, which may reveal new subsets of lymphocytes but also differences between intestinal lymphocytes in the spectrum of healthy-inflamed-tumorous colon. Intestinal lymphocytes will then be analyzed in intestinal samples from IBD patients before and after treatment with new immunomodulatory treatments. Similarly, we will also analyze intestinal samples from patients with colorectal cancer that has spread to the abdominal cavity and are being treated with chemotherapy. Our in-depth analyzes will reveal intestinal lymphocytes that may contribute to inflammation and/or cancer development in the intestine. These studies will also reveal intestinal lymphocytes that may predict or mark response to immunomodulatory therapy in IBD, and chemotherapy in metastatic CRC. This is extremely important because the right choice of effective treatment saves both individual suffering and societal costs.
  • European Research Council
    1 September 2020 - 31 August 2026
    Inflammatory bowel disease (IBD) constitutes an increasing global health burden, yet effective treatments are lacking. Hampering rationale treatment strategies, the human intestinal immune system remains largely unexplored. I have made seminal contributions to the discovery and characterization of innate lymphoid cells (ILCs) (Nat Immunol 2011, 2013 and 2016, Immunity 2012), revealing that in addition to antigen-specific adaptive T cells, innate equivalents play important roles in mucosal immunity. Determining the complementarity and redundancy of these two lymphocyte systems, acting in concert, is important for our understanding of inflammatory diseases and the development of novel therapies. For this proposal, I am in the beneficial position of having access to unique patient samples as well as established methods for single-cell RNA-sequencing to perform an ambitious and comprehensive molecular dissection of the human intestinal lymphocyte compartments in IBD. With this approach, I will determine parallels between known, and identify novel, subsets of tissue-resident, inflammation-associated, innate and adaptive lymphocytes. Building on this unprecedented molecular characterization, we will take on some of the most pressing clinical problems in IBD by performing longitudinal assessments of intestinal lymphocytes from IBD patients on conventional and biological treatments. As only a fraction of patients respond to treatment, this approach provides a golden opportunity to unveil immunological signatures of treatment response and drug-induced transformation of inflammation in non-responders. Furthermore, we will unfold critical disease mechanisms and reveal novel therapy targets and how they can be used to personalize treatment. In summary, my ambitious, yet feasible, proposal combines state-of-the-art technology with access to unique patient materials. My studies are likely to advance our understanding of the complex intestinal lymphocyte network in IBD.
  • Swedish Cancer Society
    1 January 2020
    I, along with several other research groups, have recently discovered a new cell family in the immune system. These are called "congenital lymphoid cells" (ILC) and are found in both mice and humans. ILCs are in many ways similar to T cells, whose function can be manipulated by immunotherapy in cancer, so-called check-point blockade. In mice, ILC, like T cells, plays an important role in intestinal inflammation and the development of colon cancer. However, this is unknown in humans. Furthermore, the relationship between ILC and T cells, the way these cells are regulated by the local environment in the tumor, and the way they affect tumor growth in colon cancer are hitherto unknown. The purpose of my project is to investigate the role of congenital lymphoid cells (ILC) and their relationship to T cells in colon cancer. My hypothesis is that these cells are regulated by the environment inside the tumor and also have an active role in controlling tumor growth. Through access to unique intestinal tissue samples, I can directly study ILC and T cells that are in the malignant tissue. I can determine in detail their function and thus determine what role these cells can play in colon cancer. My research will increase the understanding of the unique and complementary ways ILCs and T cells act in tumor immunity, and the way in which these cells are regulated by the tumor, but also control tumor growth in colon cancer. The purpose of my research is to find new therapy targets, associated with the interaction between cancer cells and ILC and T cells, that can be used to treat colon cancer.
  • Swedish Research Council
    1 January 2019 - 31 December 2024
  • Swedish Research Council
    1 January 2019
    Inflammatory bowel disease (IBD) constitutes an increasing global health burden. Hampering rationale treatment strategies, the human intestinal immune system remains largely unexplored. I have made seminal discoveries of innate lymphoid cells (ILC) (Nat Immunol 2011, 2013 and 2016, Immunity 2012), revealing that in addition to adaptive T cells, their innate equivalents, ILC, contribute to mucosal immunity. I am in the beneficial position of having access to unique patient samples as well as established methods for single-cell RNA-sequencing and epigenetic investigations (ATAC-seq) to perform a comprehensive molecular dissection of the human intestinal lymphocyte compartments in IBD. With this approach, we will determine functional and spatial parallels between known, and identify novel, subsets of tissue-resident, inflammation-associated, innate and adaptive lymphocytes (year 1-3). Building on this unprecedented molecular characterization, we will perform longitudinal assessments of intestinal lymphocytes from treated IBD patients (year 4-5). This approach provides a golden opportunity to unveil immunological signatures of treatment response, disease mechanisms and novel therapy targets. In summary, my ambitious, yet feasible, proposal combines state-of-the-art technology with access to unique patient materials. My established team will work closely together with clinicians and other scientists to advance our understanding of the complex intestinal lymphocyte network in IBD.

Staff and contact

Group leader

All members of the group

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
  • Anna Carrasco, PhD, postdoc
  • Luca Mazzurana, PhD student
  • Efthymia Kokkinou 

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.

Read more about our asthma research at Clinical Lung and Allergy Research Unit (CLARU).

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.