Allergens have been identified as potential triggers in patients with
atopic dermatitis (AD). Patients with AD are highly sensitive to cockroach
allergen. The underlying mechanism, however, remains undetermined. Here, we established a cockroach
allergen-induced AD-like mouse model, and we demonstrate that repeated exposure to cockroach
allergen led to aggravated mouse skin
inflammation, characterized by increased type 2 immunity, type 2 innate lymphoid cells (ILC2s), and mast cells. Increased mast cells were also observed in patients with AD. Mast cell-deficient mice (KitW-sh/W-sh) showed diminished skin
inflammation, suggesting that mast cells are required in
allergen-induced skin
inflammation. Furthermore, DC immunoreceptor (DCIR) is upregulated in skin mast cells of patients with AD and mediates
allergen binding and uptake. DCIR-/- mice or reconstituted KitW-sh/W-sh mice with DCIR-/- mast cells showed a significant reduction in AD-like
inflammation. Both in vitro and in vivo analyses demonstrate that DCIR-/- mast cells had reduced
IgE-mediated mast cell activation and passive cutaneous anaphylaxis. Mechanistically, DCIR regulates
allergen-induced
IgE-mediated mast cell ROS generation and oxidation of
calmodulin kinase II (ox-
CaMKII). ROS-resistant
CaMKII (MM-VVδ) prevents
allergen-induced mast cell activation and inflammatory mediator release. Our study reveals a DCIR/ROS/
CaMKII axis that controls
allergen-induced mast cell activation and AD-like
inflammation.