Cigarette Smoke-Induced Lymphoid Neogenesis in COPD Involves IL-17/RANKL Pathway.
Front Immunol
; 11: 588522, 2020.
Article
in En
| MEDLINE
| ID: mdl-33613513
ABSTRACT
IL-17 is critical in lung lymphoid neogenesis in COPD, but the cellular and molecular mechanisms remain to be elucidated. Receptor activator of nuclear factor-κB ligand (RANKL) functions in lymphoid follicle formation in other organs, whether it is involved in IL-17A-dependent lymphoid neogenesis in COPD is unknown. To elucidate the expression and functional role of IL-17A/RANKL pathway in COPD. We first quantified and localized RANKL, its receptor RANK and IL-17A in lungs of patients with COPD, smokers and non-smokers. Next, IL-17A-/- and wild-type (WT) mice were exposed to air or cigarette smoke (CS) for 24 weeks, and lung lymphoid follicles and RANKL-RANK expression were measured. Lastly, we studied the in vitro biological function of RANKL pertaining to lymphoid neogenesis. We found that the expressions of RANKL-RANK and IL-17A, together with lymphoid follicles, were increased in lung tissues from patients with COPD. In WT mice exposed to CS, RANKL-RANK expressions were prominent in lung lymphoid follicles, which were absent in IL-17A-/- mice exposed to CS. In the lymphoid follicles, RANKL+ cells were identified mostly as B cells and RANK was localized in dendritic cells (DCs). In vitro IL-17A increased the expressions of RANKL in B cells and RANK in DCs, which in turn responded to RANKL stimulation by upregulation of CXCL13. Altogether, these results suggest that B lymphocyte RANKL pathway is involved in IL-17A-dependent lymphoid neogenesis in COPD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Smoke
/
Nicotiana
/
Interleukin-17
/
Pulmonary Disease, Chronic Obstructive
/
RANK Ligand
/
Lymphoid Tissue
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Front Immunol
Year:
2020
Document type:
Article
Affiliation country:
China