4.8 Article

Thy1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1512600113

Keywords

lymphatic endothelial cell; pathogenic Th2 cell; IL-7; iBALT; chronic rhinosinusitis

Funding

  1. Global COE (Center of Excellence) Program (Global Center for Education and Research in Immune System Regulation and Treatment)
  2. Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) [26221305, 21390147, 24592083, 24790461, 25860352, 23890030, 25893032]
  3. Ministry of Health, Labor and Welfare
  4. Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) from the Japan Agency for Medical Research and Development
  5. Astellas Foundation for Research on Metabolic Disorders
  6. Uehara Memorial Foundation
  7. Osaka Foundation for Promotion of Fundamental Medical Research
  8. Kanae Foundation for the Promotion of Medical Science
  9. Princess Takamatsu Cancer Research Fund
  10. Takeda Science Foundation
  11. Naito Foundation
  12. Japanese Society for the Promotion of Science Postdoctoral Fellowship [2109747]
  13. AMED
  14. Grants-in-Aid for Scientific Research [16K15288, 24592083, 16H05172, 24790461, 25893032, 23890030, 25860352, 15H01153, 24111001, 26221305] Funding Source: KAKEN

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Memory CD4(+) T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. How these pathogenic memory Th cells are maintained, particularly at sites of local inflammation, remains unclear. We found that ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue (iBALT) are formed during chronic allergic inflammation in the lung, and that memory-type pathogenic Th2 (Tpath2) cells capable of driving allergic inflammation are maintained within the iBALT structures. The maintenance of memory Th2 cells within iBALT is supported by Thy1(+) IL-7-producing lymphatic endothelial cells (LECs). The Thy1(+) IL-7-producing LECs express IL-33 and T-cell-attracting chemokines CCL21 and CCL19. Moreover, ectopic lymphoid structures consisting of memory CD4(+) T cells and IL-7(+) IL-33(+) LECs were found in nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, Thy1(+) IL-7-producing LECs control chronic allergic airway inflammation by providing a survival niche for memory-type Tpath2 cells.

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