Antiapoptotic serine protease inhibitors contribute to survival of allergenic TH2 cells

Background The mechanisms that regulate maintenance of persistent T H 2 cells and potentiate allergic inflammation are not well understood. Objective The function of serine protease inhibitor 2A (Spi2A) was studied in mouse T H 2 cells, and the serine protease inhibitor B3 (SERPINB3) and SERPINB4 genes were studied in T H 2 cells from patients with grass pollen allergy. Methods Spi2A-deficient T H 2 cells were studied in in vitro culture or in vivo after challenge of Spi2A knockout mice with ovalbumin in alum. Expression of SERPINB3 and SERPINB4 mRNA was measured in in vitro –cultured T H 2 cells and in ex vivo CD27 − CD4 + cells and innate lymphoid cell (ILC) 2 from patients with grass pollen allergy by using quantitative PCR. SERPINB3 and SERPINB4 mRNA levels were knocked down in cultured CD27 − CD4 + cells with small hairpin RNA. Results There were lower levels of in vitro –polarized T H 2 cells from Spi2A knockout mice ( P in vivo after ovalbumin challenge ( P P P In vitro –polarized T H 2 cells from patients with grass pollen allergy expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P − CD4 + from patients with grass pollen allergy expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P + CD4 + cells. ILC2 expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P SERPINB3 or SERPINB4 mRNA (both P − CD4 + compared with control transduced cells. Conclusion The Serpins Spi2A in mice and SERPINB3 and SERPINB4 in allergic patients control the viability of T H 2 cells. This provides proof of principle for a therapeutic approach for allergic disease through ablation of allergic memory T H 2 cells through SERPINB3 and SERPINB4 mRNA downregulation.