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About our research

Severe asthma is a major clinical problem, and there is no curative treatment. At CLARU we have performed large biomarker studies such as the  and BIOAIR studies, which still generates invaluable disease insight through well-structured biobanks and data registers.

In the ongoing BIOCROSS (BIOmarkers in CROSS-sectional) and 3TR-ABC (asthma biologics cohort) studies, well-defined patients with severe asthma undergo repeated sampling to study both short- and long-term effects of new biological treatments. We also perform in-depth single cell analyses of lung tissues from patients with severe asthma. Such studies will increase the knowledge of the immunological landscape of the asthmatic lung and thus identify new potential treatment targets.

Group leader

Group members

Projects

TESLA (Tissue-resident lymphocytes in asthma)

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 and other tissue residing lymphocytes in asthma with particular focus on how the asthmatic lung microenvironment regulates lymphocyte function and plasticity and the effect of novel biological treatments on ILC2 and other tissue residing lymphocytes.

Our immune-characterizations are conducted using single-cell (sc) techniques such as scRNA-sequencing and multidimensional flow cytometry at our lab at the Center for Infectious Medicine (CIM).

The project is lead by Professor Jenny Mjösberg.

Defining the metabolic signatures of tissue resident human ILCs in asthma

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 in asthma. Our aim is to 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.

The project is lead by Dr Chris Tibbitt, who also conducts independent research at the Center for Infectious Medicine (CIM).

BIOCROSS (BIOmarkers in CROSS-sectional) and 3TR-ABC (asthma biologics cohort)

BIOCROSS, is a collaborative project in Sweden that studies well-characterized patients with mild and severe asthma, healthy controls and comparison groups of patients with other lung diseases.

The study approaches clinical everyday life by collecting the non-invasive samples of blood, urine, saliva and exhaled air. This is to perform a large number of analyses of the body's own substances and molecules with complementary techniques like transcriptomics, proteomics, metabolomics, lipidomics, genomics and epigenetics.

Collection of samples and molecular analyses take place according to detailed protocols and SOPs and are compiled with a broad systems biology strategy with the overall aim of discovering new biomarker profiles. This integration of information thus means that physiological and clinical measurement variables are compared with the biomarker patterns identified in blood, urine, saliva and exhaled air.

In 2023 we will start (taxonomy, treatment, targets and remission) study ABC. This study shares many features with the BIOCROSS study but is performed in an international consortium and includes tissue samples from .

The projects are lead by Professor Sven-Erik Dahlén.

Collaborations

•  
• CFA

Research support

• ̽»¨¾«Ñ¡.
• Region Stockholm.
• The 3TR study receives funding from Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 831434. 
  The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

Selected publications

1. 
   Kokkinou E, Soini T, Pandey RV, van Acker A, Theorell J, Czarnewski P, Kvedaraite E, Vandamme N, Lourda M, Sorini C, Weigel W, Carrasco A, Tibbitt CA, Schlums H, Lindforss U, Nordenvall C, Ljunggren M, Ideström M, Svensson M, Henter JI, Villablanca EJ, Bryceson YT, Rolandsdotter H, Mjösberg J
   Cell Rep Med 2023 May;4(5):101038
    
2. 
   Björkander S, Maier P, Kere M, Merid SK, Wirth L, Wiegel W, Ekström S, Kull I, Bergström A, Melén E, Mjösberg J, Tibbitt CA
   Allergy 2023 Sep;78(9):2533-2536
    
3. 
   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):eabj830
    
4. 
   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 05;31(5):554-568
    
5. 
   Hochdörfer T, Winkler C, Pardali K, Mjösberg J
   Eur J Immunol 2019 06;49(6):884-893
    
6. 
   Winkler C, Hochdörfer T, Israelsson E, Hasselberg A, Cavallin A, Thörn K, Muthas D, Shojaee S, Lüer K, Müller M, Mjösberg J, Vaarala O, Hohlfeld J, Pardali K
   J Allergy Clin Immunol 2019 07;144(1):61-69.e7
    
7. 
   Maric J, Ravindran A, Mazzurana L, Van Acker A, Rao A, Kokkinou E, Ekoff M, Thomas D, Fauland A, Nilsson G, Wheelock CE, Dahlén SE, Ferreirós N, Geisslinger G, Friberg D, Heinemann A, Konya V, Mjösberg J
   J Allergy Clin Immunol 2019 06;143(6):2202-2214.e5
    
8. 
   Maric J, Ravindran A, Mazzurana L, Björklund ÅK, Van Acker A, Rao A, Friberg D, Dahlén SE, Heinemann A, Konya V, Mjösberg J
   J Allergy Clin Immunol 2018 05;141(5):1761-1773.e6
    
9. 
   Björklund ÅK, Forkel M, Picelli S, Konya V, Theorell J, Friberg D, Sandberg R, Mjösberg J
   Nat Immunol 2016 Apr;17(4):451-60
    
10. 
    Sparreman Mikus M, Kolmert J, Andersson LI, Östling J, Knowles RG, Gómez C, Ericsson M, Thörngren JO, Emami Khoonsari P, Dahlén B, Kupczyk M, De Meulder B, Auffray C, Bakke PS, Beghe B, Bel EH, Caruso M, Chanez P, Chawes B, Fowler SJ, Gaga M, Geiser T, Gjomarkaj M, Horváth I, Howarth PH, Johnston SL, Joos G, Krug N, Montuschi P, Musial J, Niżankowska-Mogilnicka E, Olsson HK, Papi A, Rabe KF, Sandström T, Shaw DE, Siafakas NM, Uhlén M, Riley JH, Bates S, Middelveld RJM, Wheelock CE, Chung KF, Adcock IM, Sterk PJ, Djukanovic R, Nilsson P, Dahlén SE, James A,
    Eur Respir J 2022 02;59(2):
     
11. 
    Gülen T, Teufelberger A, Ekoff M, Westerberg CM, Lyberg K, Dahlén SE, Dahlén B, Nilsson G
    J Allergy Clin Immunol 2021 09;148(3):889-894