Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 20, Pages E2842-E2851Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1512600113
Keywords
lymphatic endothelial cell; pathogenic Th2 cell; IL-7; iBALT; chronic rhinosinusitis
Categories
Funding
- Global COE (Center of Excellence) Program (Global Center for Education and Research in Immune System Regulation and Treatment)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) [26221305, 21390147, 24592083, 24790461, 25860352, 23890030, 25893032]
- Ministry of Health, Labor and Welfare
- Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) from the Japan Agency for Medical Research and Development
- Astellas Foundation for Research on Metabolic Disorders
- Uehara Memorial Foundation
- Osaka Foundation for Promotion of Fundamental Medical Research
- Kanae Foundation for the Promotion of Medical Science
- Princess Takamatsu Cancer Research Fund
- Takeda Science Foundation
- Naito Foundation
- Japanese Society for the Promotion of Science Postdoctoral Fellowship [2109747]
- AMED
- 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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