TRIM33 prevents the exacerbation of allergic asthma by restricting the overactivation of alveolar macrophages.

Abstract

Alveolar macrophages (AMs) and dendritic cells (DCs) are the two major types of primary innate immune cells in allergic asthma and their functions were elaborately regulated during the progression of asthma. Tripartite motif-containing protein 33 (TRIM33) is a multifunctional protein that regulates differentiation and function of immune cells. However, its role in AMs and DCs in the context of allergic asthma remained unclear. Herein, we found that specific deletion of TRIM33 in AM and DCs (ItgaxTrim33mice) affected their homeostasis in lung and induced aggravated allergic asthma. Though reduced in number in steady state, antigen-exposed Trim33CD11bDCs exhibited comparable potency in triggering allergic asthma. Replacing Trim33AMs with normal AMs could alleviate the aggravated HDM-induced airway inflammation and Th2 responses in ItgaxTrim33mice. Moreover, Trim33AMs exhibited stronger activation status and became an additional cellular source of CCL2 when encountered the allergen, thereby promoting the recruitment of CD11bDCs into lung and draining lymph nodes where they amplifying Th2 responses in ItgaxTrim33mice. Our study revealed a crucial role of TRIM33 in controlling the aggravation of allergic asthma via repressing AM overactivation.