A unique role for IL-13 in inducing esophageal eosinophilia through MID-1 and STAT6.

Girkin, JLN; Sokulsky, LA; Starkey, MR; Hansbro, PM; Foster, PS; Collison, AM; Mattes, J

A unique role for IL-13 in inducing esophageal eosinophilia through MID-1 and STAT6.

Girkin, JLN Sokulsky, LA Starkey, MR Hansbro, PM Foster, PS Collison, AM Mattes, J

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Publisher:: FRONTIERS MEDIA SA
Publication Type:: Journal Article
Citation:: Front Allergy, 2023, 4, pp. 1248432
Issue Date:: 2023

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Field	Value	Language
dc.contributor.author	Girkin, JLN
dc.contributor.author	Sokulsky, LA
dc.contributor.author	Starkey, MR
dc.contributor.author	Hansbro, PM
dc.contributor.author	Foster, PS
dc.contributor.author	Collison, AM
dc.contributor.author	Mattes, J
dc.date.accessioned	2024-04-14T20:06:26Z
dc.date.available	2023-10-17
dc.date.available	2024-04-14T20:06:26Z
dc.date.issued	2023
dc.identifier.citation	Front Allergy, 2023, 4, pp. 1248432
dc.identifier.issn	2673-6101
dc.identifier.issn	2673-6101
dc.identifier.uri	http://hdl.handle.net/10453/177900
dc.description.abstract	INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with allergen-driven inflammation of the esophagus and an upregulated Th2 cytokine signature. Recombinant interleukin (IL)-13 (rIL-13) administration to mice induces some of the hallmark features of EoE, including increased eotaxin expression and eosinophil recruitment. Inflammation in EoE has previously been shown to depend on the expression of TRAIL and MID-1, which reduced protein phosphatase 2A (PP2A) activity. The relationship between IL-13 and TRAIL signalling in esophageal eosinophilia is currently unknown. OBJECTIVE: To investigate the interaction between IL-13-driven eosinophil infiltration and TRAIL or MID-1 in the esophagus. METHOD: We administered rIL-13 to wild type (WT), TRAIL-deficient (Tnsf10-/-) or STAT6-deficient (STAT6-/-) mice and targeted MID-1 with small interfering RNA. RESULTS: rIL-13 administration to mice increased TRAIL and MID-1 expression in the esophagus while reducing PP2A activity. TRAIL deficient, but not STAT6 deficient mice demonstrated increased MID-1 expression and PP2A reduction upon IL-13 challenge which correlated with eosinophil infiltration into the esophagus. Silencing MID-1 expression with siRNA completely ablated IL-13 induced eosinophil infiltration of the esophagus, restored PP2A activity, and reduced eotaxin-1 expression. CONCLUSION: IL-13-driven eosinophil infiltration of the esophagus induced eosinophilia and eotaxin-1 expression in a STAT6-dependent and MID-1-dependent manner. This study highlights a novel mechanism employed by IL-13 to perpetuate eosinophil infiltration.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	FRONTIERS MEDIA SA
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1079187
dc.relation	http://purl.org/au-research/grants/nhmrc/1079187
dc.relation.ispartof	Front Allergy
dc.relation.isbasedon	10.3389/falgy.2023.1248432
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	3204 Immunology
dc.title	A unique role for IL-13 in inducing esophageal eosinophilia through MID-1 and STAT6.
dc.type	Journal Article
utslib.citation.volume	4
utslib.location.activity	Switzerland
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	open_access	*
dc.date.updated	2024-04-14T20:06:14Z
pubs.publication-status	Published online
pubs.volume	4

Abstract:

INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with allergen-driven inflammation of the esophagus and an upregulated Th2 cytokine signature. Recombinant interleukin (IL)-13 (rIL-13) administration to mice induces some of the hallmark features of EoE, including increased eotaxin expression and eosinophil recruitment. Inflammation in EoE has previously been shown to depend on the expression of TRAIL and MID-1, which reduced protein phosphatase 2A (PP2A) activity. The relationship between IL-13 and TRAIL signalling in esophageal eosinophilia is currently unknown. OBJECTIVE: To investigate the interaction between IL-13-driven eosinophil infiltration and TRAIL or MID-1 in the esophagus. METHOD: We administered rIL-13 to wild type (WT), TRAIL-deficient (Tnsf10-/-) or STAT6-deficient (STAT6-/-) mice and targeted MID-1 with small interfering RNA. RESULTS: rIL-13 administration to mice increased TRAIL and MID-1 expression in the esophagus while reducing PP2A activity. TRAIL deficient, but not STAT6 deficient mice demonstrated increased MID-1 expression and PP2A reduction upon IL-13 challenge which correlated with eosinophil infiltration into the esophagus. Silencing MID-1 expression with siRNA completely ablated IL-13 induced eosinophil infiltration of the esophagus, restored PP2A activity, and reduced eotaxin-1 expression. CONCLUSION: IL-13-driven eosinophil infiltration of the esophagus induced eosinophilia and eotaxin-1 expression in a STAT6-dependent and MID-1-dependent manner. This study highlights a novel mechanism employed by IL-13 to perpetuate eosinophil infiltration.

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