The Histone Deacetylase Inhibitor Trichostatin a (TSA) Suppresses Alternaria Extract-Induced Murine Innate Allergic Inflammation By Blocking Group 2 Innate Lymphoid Cell (ILC2) Activation
Sunday, March 6, 2016: 4:45 PM
Concourse Foyer (Convention Center)
Shinji Toki, Ph.D., Kasia Goleniewska, M.S., Sara Reiss, M.S., Weisong Zhou, Ph.D., Dawn C. Newcomb, Ph.D., Melissa H. Bloodworth, B.S., Matthew T. Stier, B.S., Kelli L. Boyd, Ph.D., Vasiliy V. Polosukhin, M.D., Ph.D., Sriram Subramaniam, M.B.,B.S., R. Stokes Peebles Jr., MD FAAAAI
Rationale: Group 2 innate lymphoid cells (ILC2) are an important source of the type 2 cytokines IL-5 and IL-13 that are critical to allergic airway inflammation. Previous studies reported that histone deacetylase (HDAC) inhibition by trichostatin A (TSA) down-regulated adaptive allergic immune responses; however, the effect of HDAC inhibition on the early innate allergic immune response is unknown. We therefore tested the hypothesis that TSA treatment reduces Alternaria extract-induced early innate airway inflammation by blocking of ILC2 activation.

Methods: WT BALB/c mice were intranasally challenged with Alternaria extract for 4 consecutive days following TSA or vehicle treatment. Bronchoalveolar lavage (BAL) fluid and lung were harvested 24 hours after the last Alternaria extract-challenge. Protein expression of cytokines and chemokines in the lung were measured by ELISA. IL-5 and IL-13 expressing lung ILC2 were detected by flow cytometry. Eosinophilia and mucus production in the airway were evaluated by histopathological scoring.

Results: TSA treatment significantly decreased IL-33, a cytokine that activates lung ILC2, and the number of ILC2 expressing IL-5 and IL-13 in the lungs challenged with Alternaria extract compared to vehicle treatment. In addition, TSA treatment significantly decreased protein expression of IL-5, IL-13, eotaxin, and eotaxin-2 in the BAL fluid and lung homogenate from Alternaria extract-challenged mice. Moreover, TSA treatment significantly decreased the number of perivascular eosinophils and mucus production in the large airways that are critical components of the asthma phenotype.

Conclusions: TSA treatment reduced ILC2 activation and the early innate allergic immune responses to Alternaria extract.