Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses.
Periostin is an extracellular matrix protein that has been primarily studied in the context of the heart, where it has been shown to promote cardiac repair and remodeling. In this study, we focused on the role of periostin in an allergic eosinophilic inflammatory disease (eosinophilic esophagitis (EE)) known to involve extensive tissue remodeling. Periostin was indeed markedly overexpressed (35-fold) in the esophagus of EE patients, particularly in the papillae, compared with control individuals. Periostin expression was downstream from transforming growth factor-beta and interleukin-13, as these cytokines were elevated in EE esophageal samples and markedly induced periostin production by primary esophageal fibroblasts (107- and 295-fold, respectively, at 10 ng ml(-1)). A functional role for periostin in eliciting esophageal eosinophilia was demonstrated, as periostin-null mice had a specific defect in allergen-induced eosinophil recruitment to the lungs and esophagus (66 and 72% decrease, respectively). Mechanistic analyses revealed that periostin increased (5.8-fold) eosinophil adhesion to fibronectin. As such, these findings extend the involvement of periostin to esophagitis and uncover a novel role for periostin in directly regulating leukocyte (eosinophil) accumulation in T helper type 2-associated mucosal inflammation in both mice and humans.
Blanchard
C
C
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Mingler
M K
MK
McBride
M
M
Putnam
P E
PE
Collins
M H
MH
Chang
G
G
Stringer
K
K
Abonia
J P
JP
Molkentin
J D
JD
Rothenberg
M E
ME
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000502:physiology*; D004941:Esophagitis / Q000276:immunology* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D018793:Interleukin-13 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000473:pathology; D012220:Rhinitis / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology
D015815:Cell Adhesion Molecules; D018793:Interleukin-13; C512835:POSTN protein, human; C082838:Postn protein, mouse; D016212:Transforming Growth Factor beta