Tim Willinger group - Studying Mucosal Immunity and Inflammation In Vivo

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

Willinger Group. Photo by Tiphaine Parrot
Tim Willinger research group. Photo: Tiphaine Parrot

About our research

Inflammatory diseases of the lung are very common, such as coronavirus disease 19 (COVID-19) 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: Macrophages and innate lymphoid cells (ILCs). 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.

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Group leader

Tim Willinger

MD, PhD, Associate Professor
H7 Department of Medicine, Huddinge

Tim Willinger joined CIM in July 2015 to establish his research group at Karolinska Institutet.

Tim did his scientific training in immunology at Oxford and Yale University with Andrew McMichael and Richard Flavell. During his postdoc, he 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). He was awarded a faculty-funded career position as Senior Researcher in 2018 and became Docent in Immunology at KI in 2020.
Tim enjoys all intellectual things as well as gardening and traveling.

Group members

Natalie Sleiers

Laboratory technician
H7 Department of Medicine, Huddinge

Natalie Sleiers has been working at Karolinska Institutet and the Karolinska University Hospital for several years. She likes to spend her spare time either in the stable or the gym. Another hobby that she loves, is watching movies.

Elza Evren

PhD student
H7 Department of Medicine, Huddinge

Elza Evren 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 Alisjahbana

PhD student
H7 Department of Medicine, Huddinge

Arlisa received her Master’s Degree in in Biomedicine at Karolinska Institutet and is currently studying human lung ILCs. 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.

Previous group members

  • Helen Jongsma Wallin, Lab technician
  • Hana Kammoun, Postdoc (Marie Curie Fellow)
  • Emma Ringqvist, Postdoc
  • Imran Mohammad, Postdoc
  • Yu Gao, Postdoc
  • Johanna Emgård, PhD student
  • Linda Moet, Master student
  • Yiqi Huang, Master student
  • Inés Có, Bachelor student (ERASMUS)

Open positions

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

Collaborations

International

  • Richard Flavell (Yale University, USA)
  • James Di Santo (Pasteur Institutet, France)

At Karolinska Institutet

Projects

Development and function of human macrophages

Macrophages are the most abundant immune cells in the lung. 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. Using this model, we have recently discovered how human blood monocytes migrate and become distinct types of lung macrophages. Blood monocyte-derived macrophages are relevant in many lung diseases, including COVID-19.

KI Press Release

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 discovered that cholesterol metabolites (so-called oxysterols) guide the movement of ILCs and promote the formation of lymphoid tissue in the large intestine. Our study suggests a new possible treatment for inflammatory bowel disease.

KI Press Release

Research support

  • Karolinska Institutet (Faculty-funded position as Senior Researcher)
  • Swedish Research Council
  • SciLifeLab-KAW
  • Center for Innovative Medicine (CIMED)/Region Stockholm
  • Swedish Heart-Lung Foundation
  • Cancerfonden
  • Petrus och Augusta Hedlunds Stiftelse
  • The Royal Swedish Academy of Sciences

Selected publications

Distinct developmental pathways from blood monocytes generate human lung macrophage diversity.
Evren E, Ringqvist E, Tripathi KP, Sleiers N, Rives IC, Alisjahbana A, Gao Y, Sarhan D, Halle T, Sorini C, Lepzien R, Marquardt N, Michaëlsson J, Smed-Sörensen A, Botling J, Karlsson MCI, Villablanca EJ, Willinger T
Immunity 2021 Feb;54(2):259-275.e7

Origin and ontogeny of lung macrophages: from mice to humans.
Evren E, Ringqvist E, Willinger T
Immunology 2020 06;160(2):126-138

Metabolite Sensing by Colonic ILC3s: How Far Is Too Ffar2 Go?
Alisjahbana A, Willinger T
Immunity 2019 11;51(5):786-788

Human macrophages and innate lymphoid cells: Tissue-resident innate immunity in humanized mice.
Alisjahbana A, Mohammad I, Gao Y, Evren E, Ringqvist E, Willinger T
Biochem Pharmacol 2020 04;174():113672

Metabolic Control of Innate Lymphoid Cell Migration.
Willinger T
Front Immunol 2019 ;10():2010

Antigen-presenting ILC3 regulate T cell-dependent IgA responses to colonic mucosal bacteria.
Melo-Gonzalez F, Kammoun H, Evren E, Dutton EE, Papadopoulou M, Bradford BM, Tanes C, Fardus-Reid F, Swann JR, Bittinger K, Mabbott NA, Vallance BA, Willinger T, Withers DR, Hepworth MR
J Exp Med 2019 04;216(4):728-742

Oxysterols in intestinal immunity and inflammation.
Willinger T
J Intern Med 2019 04;285(4):367-380

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 SM, Jacob JM, Cheng HW, Evren E, Das S, Czarnewski P, Sleiers N, Melo-Gonzalez F, Kvedaraite E, Svensson M, Scandella E, Hepworth MR, Huber S, Ludewig B, Peduto L, Villablanca EJ, Veiga-Fernandes H, Pereira JP, Flavell RA, Willinger T
Immunity 2018 01;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 SM, De Camilli P, Flavell RA
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 SV, Teichmann LL, Saito Y, Marches F, Halene S, Palucka AK, Manz MG, Flavell RA
Nat Biotechnol 2014 Apr;32(4):364-72