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

Author:

Shinoda Kenta,Hirahara Kiyoshi,Iinuma Tomohisa,Ichikawa Tomomi,Suzuki Akane S.,Sugaya Kaoru,Tumes Damon J.,Yamamoto Heizaburo,Hara Takahiro,Tani-ichi Shizue,Ikuta Koichi,Okamoto Yoshitaka,Nakayama Toshinori

Abstract

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.

Funder

Ministry of Education, Culture, Sports, Science, and Technology

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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