Finally, the human and murine necroptosis inhibitor, GW806742X, blocked necroptosis and IL-33 release in vitro and reduced eosinophilia in Aspergillus fumigatus extract-induced asthma in vivo, an allergic inflammation model that is highly dependent on IL-33.
Whereas IL-33, IL-25 and thymic stromal lymphopoietin (TSLP) are involved in induction of FAP-induced ILC-mediated airway eosinophilia, IL-33-rather than IL-25 and/or TSLP-was critical for the eosinophilia in our model.
Furthermore, serum and sputum IL-33 levels were higher in COPD subjects with sputum eosinophilia than in those with a sputum eosinophil count ≤3% (p < 0.001 for both).
Interleukin-33 (IL-33) induces T helper type 2 (Th2) cytokine production and eosinophilia independently of acquired immunity, leading to innate immunity-mediated allergic inflammation.
Conversely, concomitant administration of platelets derived from wild-type mice but not IL-33-deficient mice enhanced the papain-induced airway eosinophilia.
Moreover, IL-2 produced by IL-33-stimulated MCs promoted expansion of numbers of Treg cells, thereby suppressing development of papain- or IL-33-induced airway eosinophilia.
We recruited 284 patients with NP in four participating hospitals in Belgium and 427 healthy controls, and genotyped 10 SNPs affecting eosinophilia (rs1420101 in IL1RL1, rs12619285 in IKZF2, rs4431128 in GATA2, rs4143832 in IL5, rs3184504 in SH2B3, rs2416257 in WDR36, rs2269426 in MHC, rs9494145 in MYB, rs748065 in GFRA2, and rs3939286 in IL33) using MALDI-TOF.
Furthermore, RW-immunized mice, when topically challenged with both RW and IL-33, developed more striking eosinophilia in their conjunctiva without exacerbation of the clinical AC score.