@ARTICLE{Alladina2023,
  title    = "{A human model of asthma exacerbation reveals transcriptional
              programs and cell circuits specific to allergic asthma}",
  author   = "Alladina, Jehan and Smith, Neal P and Kooistra, Tristan and
              Slowikowski, Kamil and Kernin, Isabela J and Deguine, Jacques and
              Keen, Henry L and Manakongtreecheep, Kasidet and Tantivit,
              Jessica and Rahimi, Rod A and Sheng, Susan L and Nguyen, Nhan D
              and Haring, Alexis M and Giacona, Francesca L and Hariri, Lida P
              and Xavier, Ramnik J and Luster, Andrew D and Villani,
              Alexandra-Chlo{\'e} and Cho, Josalyn L and Medoff, Benjamin D",
  abstract = "Asthma is a chronic disease most commonly associated with allergy
              and type 2 inflammation. However, the mechanisms that link airway
              inflammation to the structural changes that define asthma are
              incompletely understood. Using a human model of allergen-induced
              asthma exacerbation, we compared the lower airway mucosa in
              allergic asthmatics and allergic non-asthmatic controls using
              single-cell RNA sequencing. In response to allergen, the
              asthmatic airway epithelium was highly dynamic and up-regulated
              genes involved in matrix degradation, mucus metaplasia, and
              glycolysis while failing to induce injury-repair and antioxidant
              pathways observed in controls. IL9-expressing pathogenic TH2
              cells were specific to asthmatic airways and were only observed
              after allergen challenge. Additionally, conventional type 2
              dendritic cells (DC2 that express CD1C) and CCR2-expressing
              monocyte-derived cells (MCs) were uniquely enriched in asthmatics
              after allergen, with up-regulation of genes that sustain type 2
              inflammation and promote pathologic airway remodeling. In
              contrast, allergic controls were enriched for macrophage-like MCs
              that up-regulated tissue repair programs after allergen
              challenge, suggesting that these populations may protect against
              asthmatic airway remodeling. Cellular interaction analyses
              revealed a TH2-mononuclear phagocyte-basal cell interactome
              unique to asthmatics. These pathogenic cellular circuits were
              characterized by type 2 programming of immune and structural
              cells and additional pathways that may sustain and amplify type 2
              signals, including TNF family signaling, altered cellular
              metabolism, failure to engage antioxidant responses, and loss of
              growth factor signaling. Our findings therefore suggest that
              pathogenic effector circuits and the absence of proresolution
              programs drive structural airway disease in response to type 2
              inflammation.",
  journal  = "Science immunology",
  volume   =  8,
  number   =  83,
  pages    = "eabq6352",
  month    =  may,
  year     =  2023,
  language = "en",
  issn     = "2470-9468",
  pmid     = "37146132",
  doi      = "10.1126/sciimmunol.abq6352",
  pmc      = "PMC10440046"
}