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.
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.