Jenny Mjösberg group - Human innate lymphoid cell lab

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

Group Leader

The Jenny Mjösberg group is 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. During her postdoc period in the laboratory of Hergen Spits at the AMC in Amsterdam, Jenny Mjösberg contributed to a new field in immunology with the identification of two novel subsets of human innate lymphoid cells (ILC1 and ILC2). 

Group members

Chris joined the Jenny Mjösberg research group in February 2020. In 2022 he became leader for the team Defining the metabolic signatures of tissue resident human ILCs.

Chris' focus is on understanding ILC heterogeneity across intestinal compartments through the application of single cell technologies. Chris completed his PhD studies at Newcastle University in 2015 characterizing the influence of TCR signaling on the development of autoimmune Th17 cells.

Anne did her industrial pharmacy studies and got a Master's degree in cellular and molecular infectiology, vaccinology and therapeutic antibodies from Tours University. After that Anne was part of a research team in Limoges University where she worked one year as a research engineer. She did her PhD studies specializing in antisense oligonucleotide based gene therapy in B cell and plasma cell in Limoges University.

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. Using single cell sequencing and monoclonal antibody techniques, Chris aimed to characterize human B cell and antibody responses to an experimental universal influenza vaccine and SARS-CoV-2 infection. In the Jenny Mjösberg lab he is using similar single cell approaches to characterize intestinal lymphocytes.

Efthymia joined the Jenny Mjösberg research 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. She defended her thesis in October 2022.

Efthymia completed her Bachelor's Degree in Greece in 2014 and her Master's Degree at Stockholm University and Karolinska Institutet in 2016. In her Master's thesis, Efthymia addressed the characterization and development of regulatory T-cells (Tregs) in premature infants supplemented with probiotics.

Lorenz joined the Jenny Mjösberg research group in May 2020 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.

Previously, 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.

Whitney has been working as Lab manager in the Jenny Mjösberg lab since 2020. She 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.

Jakob joined the Jenny Mjösberg research group as a Team leader for the Autoimmune neurology team in April 2022.

Jakob conducted his PhD studies on human immunodeficiency syndromes affecting lymphocyte cytotoxicity in the Professor Yenan Bryceson research group from 2010 to 2017, in parallell with his clinical training.

After obtaining his medical license and PhD in 2017, he started working as a clinical resident at Psychiatry Southwest. In 2018, he took up a postdoctoral researcher position in the Oxford Autoimmune Neurology Group led by Professor Sarosh Irani. There, he primarily studied lymphocyte function and clonality in the context of autoimmune neurological syndromes, specifically NMDA-R, LGI1 and CASPR2 autoantibody encephalitis as well as Neuromyelitis optica.

He came back to Sweden in 2020 and took up his clinical duties at Psychiatry Southwest and a postdoctoral position in Professor Fredrik Piehls group, where he focused on immune cell phenotyping in Myasthenia gravis.

When not at work, Jakob is a keen musician and loves carpentry.

John joined the Jenny Mjösberg’s group in May 2022 to begin work on his PhD.

John studied biochemistry at the University of Oregon where he worked on the development of an amine-catalyzed Rauhut-Currier reaction during the completion of his Bachelor’s degree. From 2015-2019, he worked as a technician at Oregon Health and Science University studying the role of the selenoprotein thioredoxin reductase 1 on the control of melanin synthesis in melanocytes. In 2020 he took another position as a technician at the Fred Hutchinson Cancer Center studying tumor heterogeneity and epigenetic regulation in glioblastoma using single-cell genomic methods.

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

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.
• Peter Thelin Schmidt, Juan Arkani; Department of Medicine Solna, KI and Department of Medicine, Ersta Hospital, Stockholm, Sweden.
• Fredrik Linder; Stockholm Gastrocenter, Stockholm, Sweden.
• Helena Rolandsdotter, Erik Melén; CLINTEC, Södersjukhuset, KI and Sachs' Children and Youth Hospital, Stockholm, Sweden.
• Sven-Erik Dahlén, 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.
• 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.
• Matthew Hepworth; Division of Infection, Immunity & Respiratory Medicine (L5), Division of Immunology, Immunity to Infection and Respiratory Medicine, The University of Manchester.
• 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.

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.

Selected publications

1. CD45RA+CD62L- ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs.
   Kokkinou E, Pandey RV, Mazzurana L, Gutierrez-Perez I, Tibbitt CA, Weigel W, Soini T, Carrasco A, Rao A, Nagasawa M, Bal SM, Jangard M, Friberg D, Lindforss U, Nordenvall C, Ljunggren M, Haapaniemi S, Keita ÅV, Söderholm J, Hedin C, Spits H, Bryceson YT, Mjösberg J
   Sci Immunol 2022 04;7(70):eabj8301
    
2. 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.
    
3. 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.
    
4. 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.
    
5. 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.
    
6. 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
    
7. 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.
    
8. 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. 
    
9. The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells.
   Mjösberg J, Bernink J, Golebski K, Karrich JJ, Peters CP, Blom B, te Velde AA, Fokkens WJ, van Drunen CM, Spits H
   Immunity 2012 Oct;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.