biostudies-literatureUnknown13Tomiaki CAsthma is airway inflammatory diseases caused by the activation of group 2 innate lymphoid cells (ILC2s) and type 2 helper T (T_H2) cells. Cysteine proteases allergen cause tissue damage to airway epithelial cells and activate ILC2-mediated type 2 airway inflammation. FK506 is an immunosuppressive agent against calcium-dependent NFAT activation that is also effective against asthmatic inflammation. However, the effects of FK506 on cysteine protease allergen-mediated airway inflammation remain unclear. In this study, we investigated the suppressive effects of FK506 on airway inflammation. FK506 had a partial inhibitory effect on ILC2-dependent eosinophil inflammation and a robust inhibitory effect on T cell-dependent eosinophil inflammation in a cysteine protease-induced mouse asthma model. The infiltration of T1/ST2⁺ CD4 T cells in the lungs contributed to the persistence of eosinophil infiltration in the airway; FK506 completely inhibited the infiltration of T1/ST2⁺ CD4 T cells. In the initial phase, FK506 treatment targeted lung ILC2 activation induced by leukotriene B₄ (LTB₄)-mediated calcium signaling, but not IL-33 signaling. FK506 also inhibited the IL-13-dependent accumulation of T1/ST2⁺ CD4 T cells in the lungs of the later responses. These results indicated that FK506 potently suppressed airway inflammation by targeting ILC2 activation and T1/ST2⁺ CD4 T cell accumulation.Frontiers in immunology1014462https://www.ebi.ac.uk/biostudies/studies/S-EPMC9683035biostudies-literatureRole of FK506-sensitive signals in asthmatic lung inflammation.PMC9683035Miyauchi KKi SMukoyama YMorimoto HSuzuki NSuzuki YKubo MTomiaki CfalseRole of FK506-sensitive signals in asthmatic lung inflammation.Asthma is airway inflammatory diseases caused by the activation of group 2 innate lymphoid cells (ILC2s) and type 2 helper T (T_H2) cells. Cysteine proteases allergen cause tissue damage to airway epithelial cells and activate ILC2-mediated type 2 airway inflammation. FK506 is an immunosuppressive agent against calcium-dependent NFAT activation that is also effective against asthmatic inflammation. However, the effects of FK506 on cysteine protease allergen-mediated airway inflammation remain unclear. In this study, we investigated the suppressive effects of FK506 on airway inflammation. FK506 had a partial inhibitory effect on ILC2-dependent eosinophil inflammation and a robust inhibitory effect on T cell-dependent eosinophil inflammation in a cysteine protease-induced mouse asthma model. The infiltration of T1/ST2⁺ CD4 T cells in the lungs contributed to the persistence of eosinophil infiltration in the airway; FK506 completely inhibited the infiltration of T1/ST2⁺ CD4 T cells. In the initial phase, FK506 treatment targeted lung ILC2 activation induced by leukotriene B₄ (LTB₄)-mediated calcium signaling, but not IL-33 signaling. FK506 also inhibited the IL-13-dependent accumulation of T1/ST2⁺ CD4 T cells in the lungs of the later responses. These results indicated that FK506 potently suppressed airway inflammation by targeting ILC2 activation and T1/ST2⁺ CD4 T cell accumulation.2022-01-01T00:00:00Z20222024-11-12T01:59:17.843Z2024-11-12T01:59:17.843ZS-EPMC96830353643913310.3389/fimmu.2022.1014462