Tissue resident lymphocytes in severe asthma and biologics treatment

Biologics targeting type 2 cytokines offer new hope for patients 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 biologics. Innate lymphoid cells type 2 (ILC2) and type 2 T cells (Th2 and Tc2), orchestrate type 2 inflammation.

I will build on our unexpected finding that treatment with anti-interleukin (IL)-5 biologics causes an increase in circulating type 2 lymphocytes, implying biologics effects on lymphocyte trafficking, differentiation, and tissue residency.

To test this hypothesis, I will capitalize on leading a clinical asthma research unit and immunology lab, enabling us to perform pioneering immunological studies using unique airway tissue samples from patients with severe asthma before and during biologics treatment.

My translational team of clinical, immunological and computational researchers will determine 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 mechanisms involved in lymphocyte trafficking and differentiation in the airways.

This will increase the understanding of human airway lymphocyte diversification, trafficking, tissue residency and differentiation in relation to biologics treatment efficacy. Our studies will reveal new targets for treatment and means to better tailor the use of biologics.