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

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

LanguageEnglish
PagesE2842-E2851
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number20
DOIs
Publication statusPublished - 17 May 2016

Keywords

  • Chronic rhinosinusitis
  • IBALT
  • IL-7
  • Lymphatic endothelial cell
  • Pathogenic Th2 cell

ASJC Scopus subject areas

  • General

Cite this

Shinoda, Kenta ; Hirahara, Kiyoshi ; Iinuma, Tomohisa ; Ichikawa, Tomomi ; Suzuki, Akane S. ; Sugaya, Kaoru ; Tumes, Damon ; Yamamoto, Heizaburo ; Hara, Takahiro ; Tani-Ichi, Shizue ; Ikuta, Koichi ; Okamoto, Yoshitaka ; Nakayama, Toshinori. / Thy1+ IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 20. pp. E2842-E2851.
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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.",
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author = "Kenta Shinoda and Kiyoshi Hirahara and Tomohisa Iinuma and Tomomi Ichikawa and Suzuki, {Akane S.} and Kaoru Sugaya and Damon Tumes and Heizaburo Yamamoto and Takahiro Hara and Shizue Tani-Ichi and Koichi Ikuta and Yoshitaka Okamoto and Toshinori Nakayama",
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Shinoda, K, Hirahara, K, Iinuma, T, Ichikawa, T, Suzuki, AS, Sugaya, K, Tumes, D, Yamamoto, H, Hara, T, Tani-Ichi, S, Ikuta, K, Okamoto, Y & Nakayama, T 2016, 'Thy1+ IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 20, pp. E2842-E2851. https://doi.org/10.1073/pnas.1512600113

Thy1+ IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation. / Shinoda, Kenta; Hirahara, Kiyoshi; Iinuma, Tomohisa; Ichikawa, Tomomi; Suzuki, Akane S.; Sugaya, Kaoru; Tumes, Damon; Yamamoto, Heizaburo; Hara, Takahiro; Tani-Ichi, Shizue; Ikuta, Koichi; Okamoto, Yoshitaka; Nakayama, Toshinori.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 20, 17.05.2016, p. E2842-E2851.

Research output: Contribution to journalArticle

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T1 - Thy1+ IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

AU - Shinoda, Kenta

AU - Hirahara, Kiyoshi

AU - Iinuma, Tomohisa

AU - Ichikawa, Tomomi

AU - Suzuki, Akane S.

AU - Sugaya, Kaoru

AU - Tumes, Damon

AU - Yamamoto, Heizaburo

AU - Hara, Takahiro

AU - Tani-Ichi, Shizue

AU - Ikuta, Koichi

AU - Okamoto, Yoshitaka

AU - Nakayama, Toshinori

PY - 2016/5/17

Y1 - 2016/5/17

N2 - 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.

AB - 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.

KW - Chronic rhinosinusitis

KW - IBALT

KW - IL-7

KW - Lymphatic endothelial cell

KW - Pathogenic Th2 cell

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DO - 10.1073/pnas.1512600113

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