Significance: A substantial proportion of people have intractable chronic allergic diseases for which no curative treatment exists. A clear understanding of how these allergic diseases develop and persist is lacking. Here, unique ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue were found to be formed during chronic airway inflammation, and were critical in persistent inflammation. In addition, we identified a Thy1⁺IL-7⁺IL-33⁺subset of lymphatic endothelial cells (LECs) that support the maintenance of memory-type pathogenic T helper 2 (Tpath2) cells. A similar population of IL-7⁺IL-33⁺LECs was found in nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, we revealed that Thy1⁺IL-7–producing LECs control chronic allergic airway inflammation by supporting memory-type Tpath2 cells in human and mouse systems.

Recent decades have witnessed a rapid worldwide increase in chronic inflammatory disorders such as asthma. CD4⁺ T helper 2 cells play critical roles in the pathogenesis of allergic airway inflammation, and CD69 expression on activated CD4 T cells is required to induce allergic inflammation in tissues. However, how CD69 mechanistically controls allergic inflammation remains poorly defined. In lymphoid tissues, CD69 regulates cellular retention through inhibition of S1P1 expression and requires no specific ligands to function. In contrast, we show herein that myosin light chain (Myl) 9 and Myl12 are new functional ligands for CD69. Blockade of CD69-Myl9/12 interaction ameliorates allergic airway inflammation in ovalbumin-induced and house dust mite–induced mouse models of asthma. Within the inflamed mouse airways, we found that the expression of Myl9/12 was increased and that platelet-derived Myl9/12 localized to the luminal surface of blood vessels and formed intravascular net-like structures. Analysis of nasal polyps of eosinophilic chronic rhinosinusitis patients revealed that Myl9/12 expression was increased in inflammatory lesions and was distributed within net-like structures in the intravascular space. In addition, we detected Myl9/12 in perivascular spaces where many CD69⁺ cells were positioned within Myl9/12 structures. Thus, CD69-Myl9/12 interaction is a key event in the recruitment of activated CD69⁺ T cells to inflamed tissues and could be a therapeutic target for intractable airway inflammatory diseases.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.