Tim Willinger group

Tim Willinger, CIM

Studying Mucosal Immunity and Inflammation In Vivo

My research group studies immune responses in the mucosal tissues gut and lung. We want to understand how the immune system helps maintain healthy organ function and how disturbed immune function causes chronic tissue inflammation.

Inflammatory diseases of the intestine and lung are very common, such as inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD). However, today no cure is available for these important human diseases.

Our studies focus on two types of tissue-resident immune cells that carry out specialized functions to maintain organ homeostasis: Innate lymphoid cells (ILCs) and macrophages. These cells sense and respond to signals from their environment, such as microbes, dietary factors, and metabolites. To make our studies relevant to humans, we have developed innovative models that allow us to study the cells and function of the human immune system in vivo.

Projects

Innate lymphoid cell migration

ILCs are a recently described family of immune cells that are enriched in tissues interacting with the outside world. We are particularly interested in how ILCs migrate within the body and to sites of inflammation. We have recently discovered that cholesterol metabolites (so-called oxysterols) guide the movement of ILCs and promote the formation of lymphoid tissue in the large intestine. Article in Immunity 

Oxysterols guide gut immune cells and are involved in inflammatory bowel disease

ILCs & B cells in gut lymphoid tissue express the oxysterol receptor GPR183 (green)

Cover Immunity. Photo: Johanna Emgård

Development and function of human macrophages

Macrophages are the most abundant immune cells in the airways. Due to their strategic location, they protect us from airborne pathogens, while performing tissue repair after injury or infection. However, not much is known about the development and function of lung macrophages in humans. To overcome this limitation, we have created a unique model to study human macrophages in vivo. More info
Development and function of human innate immune cells in a humanized mouse model

Human lung macrophagesUnderstanding the development of lung macrophages will provide important information that is relevant to human diseases like COPD, asthma, influenza infection, and tuberculosis.

 

 

 

Image by Nature Biotechnology (Credit: © tiripero iStock)

Funding

Center for Innovative Medicine (CIMED), Karolinska Institutet/SLL

Swedish Research Council (Vetenskapsrådet)

Åke Wibergs Stiftelse

European Union (Horizon 2020)

Collaborations

International

Richard Flavell (Yale University, USA)

Henrique Veiga-Fernandes (Champalimaud Center, Portugal)

Burkhard Ludewig (Institute of Immunobiology, Switzerland)

João Pereira (Yale University, USA)

Lucie Peduto (Pasteur Institute, France)

Matthew Hepworth (Manchester University, UK)

Samuel Huber (Hamburg University, Germany)

At Karolinska Institutet

Magnus Westgren (Department of Obstetrics & Gynecology)

Apostolos Bossios (Department of Respiratory Medicine, Huddinge)

Eduardo Villablanca (Department of Medicine, Solna)

Anna Smed Sörensen (Department of Medicine, Solna)

Members

 Tim Willinger, MD, PhD, Group Leader

He was awarded a PhD in 2006 for his work on human T cell memory in the lab of Prof. Andrew McMichael at the Weatherall Institute of Molecular Medicine in Oxford. He then moved to Yale University for his postdoctoral training with Prof. Richard Flavell in one of the leading immunology laboratories in the world. As a postdoctoral fellow, Dr. Willinger developed novel experimental models to study the human immune system in vivo (Cell Host Microbe 2010, PNAS 2011, Trends Immunol 2011, Nat Biotechnol 2014). He also identified molecular mechanisms that regulate T lymphocyte homeostasis and migration (PNAS 2012, JEM 2014, PNAS 2015). In July 2015, Dr. Willinger joined the Center for Infectious Medicine at Karolinska Institutet to continue his research on the human immune system, focusing on immune responses in the gut and lung. He is also a Junior Investigator at the Center for Innovative Medicine (CIMED).

 

Natalie Sleiers, Laboratory technician

Natalie has been working at Karolinska Institutet/Karolinska Sjukhuset for several years. She likes to spend her spare time either in the stable or the gym. She also loves to watch movies, another big hobby of her.

 

Elza Evren, PhD student

Elza received her Master’s Degree in Immunology from University Pierre and Marie Curie, France, in 2016. She did her master’s thesis in Harvard Medical School where she studied poly-N-acetyl-glucosamine, a bacterial capsule polysaccharide that provides a potentially broad-spectrum target for vaccination. She is fond of travelling, exploring new cultures and learning from past stories.

 

Arlisa AlisjahbanaArlisa Alisjahbana, Master student

Arlisa is in her final year of the Master Program in Biomedicine at KI, and is currently studying human lung ILCs for her Master thesis. Before coming to KI, she worked with tuberculosis diagnostic methods in the TB-HIV Research Center at Universitas Padjajaran (UNPAD) Bandung, Indonesia. She is an avid reader of novels, history and popular science books and enjoys visiting museums.

 

Yiqi HuangYiqi Huang, Master student

Yiqi received her BSc in Biochemistry at Imperial College London, England and started her master’s study in Biomedicine at KI last August with the KI Global Master’s Scholarship. During her bachelor’s, she has also worked for one year in Prof. Manfred Kopf’s lab at ETH Zürich, where she studied the development of alveolar macrophages and the role of interferon-transduced transmembrane protein 3 in anti-viral defense. Afterwards, she did her bachelor’s thesis in Prof. Murray Selkirk’s lab on vaccines against gastrointestinal nematode parasites. She loves cooking and enjoys delicious food, as well as playing the piano.

 

Previous members

Helen Jongsma Wallin, Lab technician

Hana Kammoun, Postdoc (Marie Curie Fellow)

Johanna Emgård, PhD student

Linda Moet, Master student

Inés Có, Bachelor student (ERASMUS)

 

Selected publications

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.
Emgård J, Kammoun H, García-Cassani B, Chesné J, Parigi S, Jacob J, et al
Immunity 2018 Jan;48(1):120-132.e8

Dynamin 2-dependent endocytosis sustains T-cell receptor signaling and drives metabolic reprogramming in T lymphocytes.
Willinger T, Staron M, Ferguson S, De Camilli P, Flavell R
Proc. Natl. Acad. Sci. U.S.A. 2015 Apr;112(14):4423-8

Development and function of human innate immune cells in a humanized mouse model.
Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty S, Teichmann L, et al
Nat. Biotechnol. 2014 Apr;32(4):364-72

Dynamin 2-dependent endocytosis is required for sustained S1PR1 signaling.
Willinger T, Ferguson S, Pereira J, De Camilli P, Flavell R
J. Exp. Med. 2014 Apr;211(4):685-700

Human hemato-lymphoid system mice: current use and future potential for medicine.
Rongvaux A, Takizawa H, Strowig T, Willinger T, Eynon E, Flavell R, et al
Annu. Rev. Immunol. 2013 ;31():635-674

Canonical autophagy dependent on the class III phosphoinositide-3 kinase Vps34 is required for naive T-cell homeostasis.
Willinger T, Flavell R
Proc. Natl. Acad. Sci. U.S.A. 2012 May;109(22):8670-5

Improving human hemato-lymphoid-system mice by cytokine knock-in gene replacement.
Willinger T, Rongvaux A, Strowig T, Manz M, Flavell R
Trends Immunol. 2011 Jul;32(7):321-7

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung.
Willinger T, Rongvaux A, Takizawa H, Yancopoulos G, Valenzuela D, Murphy A, et al
Proc. Natl. Acad. Sci. U.S.A. 2011 Feb;108(6):2390-5

Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo.
Rongvaux A, Willinger T, Takizawa H, Rathinam C, Auerbach W, Murphy A, et al
Proc. Natl. Acad. Sci. U.S.A. 2011 Feb;108(6):2378-83

A mouse model for the human pathogen Salmonella typhi.
Song J, Willinger T, Rongvaux A, Eynon E, Stevens S, Manz M, et al
Cell Host Microbe 2010 Oct;8(4):369-76

Open positions

We are looking for talented and highly motivated students and postdocs to join our new research group. To apply, submit cover letter, CV with publication list, and contact information of three references to the group leader Tim Willinger (tim.willinger@ki.se).