Congratulations, Dane!!

Congratulations to all!

Thank you Maile!

This work took a village: Thanks Vijay, Filiz, Carolina and team for help with experiments. Thanks to collabs: Alan Fine, Josh Welch, Felicia Chen, Anna C Belkina, and most importantly my postdoc advisor and lifelong mentor, Jay Mizgerd for support towards this non-pneumonia story 😁! (n/n) 🍾🎉🥳

An added bonus: our model uses C57 mice and Ova as an allergen hence all commercial immunological tools and mouse lines can be used to really unravel the disease biology and expedite our trajectory to good therapeutic options for patients affected by this morbid disease. (8/n)

Overall, this model has been kind to us by providing many new biological insights which were reliably found in human airway scRNA-Seq datasets. We hope other labs will find this model useful too! (7/n)

Interestingly, these mucus secretory cells are also key antigen presenting cells in such lungs with allergy. Using MHC-II, they (in their attempt to quell inflammation) support TH1 TRM cells which then (via IFNg) inhibit type 3 inflammation driven by the pathogenic TH17 TRM cells!! (6/n)

These mice with extensive lung histories revealed multiple mechanistic insights including a role for a novel RORgt-low TH17 TRM cell that coaxes the airway mucus secretory epithelial cells to call in neutrophils! (5/n)

In addition to recapitulating stable airway neutrophilia, plasma leakage in airways, and airway hyperreactivity (data in the paper), this model was also maintained high airway neutrophilia despite prophylacatic dexamethasone (revision data that did not make it in the paper)! (4/n)

Here, inspired by Lalit Beura's "wild vs lab mice" work
@Dave Maopust's lab, we asked if repeated but transient airborne allergen exposure in SPF mice 🐭 would instill adult human like biology and mimic neutrophilic allergic airways disease in mice. Turns out, it does! (3/n)

Neutrophilic asthma is a vexing disease due to its steroid-resistance. A barrier to mechanistic understanding and therapeutic development against this airway disease has been a lack of animal models. (2/n)

Yes. same here!