To address this issue, we (i) established a mimicking in vitro system using CD34+ hematopoietic stem cells derived LC [32], (ii) analyzed and confirmed the desensitization of LC and analyzed its underlying mechanisms in the TLR2‐NF‐κB pathway, (iii) showed that LC under these conditions can serve as a source of AD‐related cytokines, thus contributing to AD immune dysregulation, and (iv) showed evidence supporting a new putative mode of action of JAK inhibitors within the context of impaired TLR engagement in LC in AD. The gene discussed is TLR2; the disease is Alzheimer disease.