Conjunctival transcriptome analysis reveals the overexpression of multiple pattern recognition receptors in vernal keratoconjunctivitis.
CLEC4E
CLEC7A
NLRP3
NOD2
Pattern recognition receptors
TLR4
Transcriptomics
Vernal keratoconjunctivitis
Journal
The ocular surface
ISSN: 1937-5913
Titre abrégé: Ocul Surf
Pays: United States
ID NLM: 101156063
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
19
03
2020
revised:
11
09
2020
accepted:
22
09
2020
pubmed:
26
10
2020
medline:
25
6
2021
entrez:
25
10
2020
Statut:
ppublish
Résumé
Vernal keratoconjunctivitis (VKC) is a chronic, potentially blinding ocular allergic disease affecting children with uncertain pathogenic mechanisms. To identify differences in gene expression between VKC and normal subjects (CT) and to evaluate the expression of pattern recognition receptors (PRRs). Conjunctival cells were collected by impression cytology device from 25 VKC patients and 10 CT. Isolated RNA was assayed with the NanoString human immunology codeset to evaluate the expression levels of immunology-related genes. Of the 579 genes, 398 were detected and 58 were significantly differently expressed in VKC compared to CT. The number of significantly differentially expressed genes (DEG) in the 3 different phenotypes vs CT were 149 in tarsal, 17 in limbal and 68 in the mixed form of VKC. The list of the most overexpressed genes included several chemokines (CCL24, CCL18, CCL22, CXCL1), proinflammatory cytokines (IL-1β, IL-6, IL-8, TGFβ-1) and genes related to Th2- and Th17-signaling families. Toll like receptors (TLR)4 and TLR8, Dectin-1/CLEC7A, mincle/CLEC4E, MCR1, NOD2 and NLRP3 and several of their pathway-related genes were significantly overexpressed in VKC. The number of DEG increased with the disease severity either in IgE+ or IgE- patients. Immunohistochemistry analysis of VKC conjunctival tissues confirmed an increased expression of these molecules at protein level. The increased expression of several chemotactic factors and co-stimulatory signals required for T-cell activation, confirms that VKC is mostly cell-mediated with local eosinophilia. The multiple expression of PRRs suggests a role of host-pathogens interaction in VKC development.
Sections du résumé
BACKGROUND
Vernal keratoconjunctivitis (VKC) is a chronic, potentially blinding ocular allergic disease affecting children with uncertain pathogenic mechanisms.
OBJECTIVE
To identify differences in gene expression between VKC and normal subjects (CT) and to evaluate the expression of pattern recognition receptors (PRRs).
METHODS
Conjunctival cells were collected by impression cytology device from 25 VKC patients and 10 CT. Isolated RNA was assayed with the NanoString human immunology codeset to evaluate the expression levels of immunology-related genes.
RESULTS
Of the 579 genes, 398 were detected and 58 were significantly differently expressed in VKC compared to CT. The number of significantly differentially expressed genes (DEG) in the 3 different phenotypes vs CT were 149 in tarsal, 17 in limbal and 68 in the mixed form of VKC. The list of the most overexpressed genes included several chemokines (CCL24, CCL18, CCL22, CXCL1), proinflammatory cytokines (IL-1β, IL-6, IL-8, TGFβ-1) and genes related to Th2- and Th17-signaling families. Toll like receptors (TLR)4 and TLR8, Dectin-1/CLEC7A, mincle/CLEC4E, MCR1, NOD2 and NLRP3 and several of their pathway-related genes were significantly overexpressed in VKC. The number of DEG increased with the disease severity either in IgE+ or IgE- patients. Immunohistochemistry analysis of VKC conjunctival tissues confirmed an increased expression of these molecules at protein level.
CONCLUSIONS
The increased expression of several chemotactic factors and co-stimulatory signals required for T-cell activation, confirms that VKC is mostly cell-mediated with local eosinophilia. The multiple expression of PRRs suggests a role of host-pathogens interaction in VKC development.
Identifiants
pubmed: 33098984
pii: S1542-0124(20)30149-X
doi: 10.1016/j.jtos.2020.09.009
pii:
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
241-248Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.