Sensory Neurons Promote Immune Homeostasis in the Lung

Cytokines employ downstream Janus kinases (JAKs) to promote many chronic inflammatory disorders. JAK1-dependent type 2 cytokines drive allergic inflammation and patients with JAK1 gain-of-function (GOF) variants develop atopic dermatitis (AD) and asthma. To explore the tissue-specific role of JAK1, we inserted a human JAK1 GOF variant into mice and observed the spontaneous development of AD-like skin inflammation but unexpected resistance to allergic lung inflammation when JAK1 GOF expression was restricted to the stroma. Further, we identified the chemical denervation of both vagal and spinal visceral afferents exacerbated allergic lung inflammation, though selective denervation of spinal visceral afferent did not change the disease severity compared to control groups. Collectively, we suggested that neuron-intrinsic JAK1 in the vagal afferents protect against allergic lung inflammation. Comparative gene expression profiling analysis of RNA-seq data for mouse lung of control and experimental samples. (Bone marrow (BM) chimeric mice [wild-type (WT)_to_WT mice vs. WT_to_human JAK1 GOF mice], selective denervation of spinal visceral afferents [intrathecal vehicle injection vs. intrathecal resiniferatoxin injection], systemic denervation of both vagal and spinal visceral afferents [subcutaneous vehicle injection vs. subcutaneous resiniferatoxin injection])