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Targeting airway lymphocytes in asthma and biologics treatment

Project description

Improving severe asthma treatment

Severe asthma affects millions of people worldwide, and while new biologic therapies have brought hope, many patients do not respond to them. Understanding why requires deeper insight into how immune cells behave in airway tissues and how biologics affect them. The ERC-funded TARGET-AIR-LAB project investigates the role of type 2 lymphocytes that are implicated in airway inflammation. Researchers will elucidate how biologic treatments alter the movement, differentiation and function of type 2 lymphocytes using unique airway tissue samples from asthma patients before and during treatment. The project will also provide insight into the epigenetic and transcriptional changes that biologics induce in these cells. Results are expected to reveal new therapeutic targets and strategies for tailoring biologic treatments, ultimately improving clinical outcome.

Objective

The development of biologics targeting cytokines involved in type 2 lymphocyte function and activation offers new hope for more than 16 million patients living with severe asthma, but not all patients respond, and none are cured. This calls for increased understanding of airway tissue type 2 lymphocytes and how they are regulated by novel biologics in severe asthma. I discovered human innate lymphoid cells type 2 (ILC2), and have shown how they, in addition to T helper 2 (Th2) cells, orchestrate type 2 immunity in tissues. Building on our unexpected finding that treatment with anti-interleukin (IL)-5 biologics causes an increase in circulating type 2 lymphocytes with modified tissue homing receptor expression, I propose that biologics disrupt airway chemoattractants, lymphocyte trafficking, differentiation, and function, including the underlying epigenetic, transcriptional and functional regulation. To test this innovative hypothesis, I will capitalize on leading a clinical asthma research unit, performing pioneering immunological studies using unique airway tissue samples from patients with severe asthma before and during biologics treatment. My translational team of clinical, immunology and computational researchers will uncover the unique features of airway resident lymphocytes and the epigenetic and transcriptional effects of biologics on circulating and airway resident lymphocytes. We will also dissect the molecular and functional mechanisms involved in lymphocyte trafficking and differentiation in the airways. My studies will break new ground by increased understanding of human airway lymphocyte diversification, trafficking, differentiation and function in relation to biologics treatment efficacy. I will thereby reveal new targets for treatment and means to better tailor the use of biologics. Building on the outcomes of this proposal, my long-term goal is to advance the possibilities for induction of remission in severe asthma by targeting airway lymphocytes.

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HORIZON-ERC - HORIZON ERC Grants

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(opens in new window) ERC-2025-COG

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Host institution

KAROLINSKA INSTITUTET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 999 008,00
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 999 008,00

Beneficiaries (1)

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