Melissa Parker

The adaptor molecule DNAX-activating protein of 12 kDa (DAP12) is broadly expressed in innate immune cells, but its role in autoimmunity remains unclear due to its dual regulatory functions. We investigated the contribution of the DAP12 pathway to bullous pemphigoid (BP), the most common autoimmune blistering disease, using a mouse model induced by transfer of anti-type XVII collagen (Col17) IgG. Repeated anti-Col17 IgG injections over 12 days produced comparable disease activity in DAP12-deficient and wildtype mice (n = 17/group), indicating that disease induction occurs independently of DAP12 signaling. Flow cytometry and immunofluorescence analysis of lesional skin further revealed a strong upregulation of the DAP12-associated triggering receptors expressed on myeloid cells (TREM) 1 in wildtype BP lesions, whereas TREM2⁺ cell frequencies in anti-Col17 IgG-treated wildtype and DAP12 knock-out animals were significantly lower than in healthy controls. Additional flow cytometry analysis demonstrated altered inflammatory infiltrates with notably reduced frequencies of Siglec-f⁺ eosinophils in DAP12-deficient vs. wildtype lesional skin. In addition, pharmacological inhibition of PI3Kδ, a downstream kinase of the DAP12/TREM pathway, did not affect disease progression in anti-Col17 IgG-induced BP. Collectively, these findings indicate that while DAP12 signaling modulates local immune cell composition, the DAP12/TREM1/2-axis does not influence overall disease activity in experimental BP.

Allergic contact dermatitis is driven by an overreaction of the body's immune system to a normally harmless substance resulting in skin inflammat |

Atopic dermatitis (AD) is characterized by intense itch and recurrent eczematous lesions. Interleukin (IL)-33 is constitutively produced from the |

Phosphatidylinositol-3-kinase (PI3K) delta-dependent pathways are essential for immune cell activation. Targeting PI3K-delta has beneficial effect in several preclinical models of inflammatory disorders. PI3K-delta contributes to T and B cell development, survival, and antigen recognition as well as various neutrophil functions. Here, we investigated the effect of INCB050465, a