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Proc Natl Acad Sci U S A. 2016 May 17;113(20):E2842-51. doi: 10.1073/pnas.1512600113. Epub 2016 May 2.

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

Author information

1
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;
2
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;
3
Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;
4
Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;
5
Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;
6
Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan;
7
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; AMED-CREST, AMED, Chiba 260-8670, Japan tnakayama@faculty.chiba-u.jp.

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.

KEYWORDS:

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

PMID:
27140620
PMCID:
PMC4878506
DOI:
10.1073/pnas.1512600113
[Indexed for MEDLINE]
Free PMC Article

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