Effects of blocking TSLP on ILC and T cell subpopulations in patients with asthma

Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine known to trigger T2 inflammation in asthma through the activation of type 2 T helper cells (Th2) and group 2 innate lymphoid cells (ILC2). Previous studies found no effect of anti-TSLP on Th2 or T regulatory cells (Treg) thus, a broader investigation of the immune-cellular effects of anti-TSLP and more specifically ILC2 are warranted. The aim of the study was to investigate the relationship between serum TSLP and ILC/T cell populations, and to study the effect of anti-TSLP on ILC/T cell populations in asthma patients. Asthma patients were randomized to either 700mg Tezepelumab (anti-TSLP) or placebo every 4 weeks for 12 weeks. Serum TSLP was measured and ILC/T cell populations (ILC1, ILC2, ILC3, Th1 CD4+, Th2 CD4+, Th17 CD4+, Treg CD4+, T-bet CD8+, INFγ+ CD4+, INFγ+ CD8+) were investigated by flow cytometry (gated by surface markers, transcriptions factors and cytokine) from peripheral blood mononuclear cells isolated at baseline and week-12. Flow cytometry data were available in 31 patients at baseline and week-12 (15 on anti-TSLP and 16 on placebo). Baseline serum TSLP did not correlate with ILC2 but correlated negatively with ILC3 (r_s=-.419, p<.05) and positively with INFy+ CD8+ cells (r=.371, p<.05). No changes from baseline to week-12 were found in ILC2 or any other cell populations in respectively placebo and anti-TSLP treated patients. Blocking TSLP does not change the circulating pool of ILC/T cell populations in asthma patients. Further studies on TSLP and ILC/T cell function and ILC/T cell populations in the airways are warranted.