Mucosal Immunol. 2025 Jul 16:S1933-0219(25)00074-1. doi: 10.1016/j.mucimm.2025.07.003. Online ahead of print.
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 (ItgaxCre-GFPTrim33fl/fl mice) affected their homeostasis in lung and induced aggravated allergic asthma. Though reduced in number, TRIM33 deficient CD11b± DCs exhibited comparable potency in triggering allergic asthma. Replacing Trim33-/- AMs with normal AMs could alleviate the aggravated HDM-induced airway inflammation and Th2 responses in ItgaxCre-GFPTrim33fl/fl mice. Moreover, Trim33-/- AMs exhibited stronger activation status and became an additional cellular source of CCL2 when encountered the allergen, thereby promoting the recruitment of CD11b+ DCs into lung and draining lymph nodes where they amplifying Th2 responses in ItgaxCre-GFPTrim33fl/fl mice. Our study revealed a crucial role of TRIM33 in controlling the aggravation of allergic asthma via repressing AM overactivation.
PMID:40681151 | DOI:10.1016/j.mucimm.2025.07.003