Background
CCL19 has been shown to predict disease severity in COVID-19 and treatment response in rheumatoid arthritis. CCL19 can exert both pro- and anti-inflammatory effects and is elevated in chronic rhinosinusitis (CRS). However, its role in CRS remains unknown. This study sought to determine the transcriptional changes in CCL19, its receptors, and associated cytokines and their association with disease severity in CRS.
Methods
A clinical database of control subjects and patients with CRS was examined. Lund-Kennedy, Lund-Mackay, Sinonasal Outcomes Test 22 (SNOT-22), and rhinosinusitis disability index (RSDI) scores were collected at enrollment. mRNA was extracted from sinonasal tissues and subjected to multiplex gene expression analysis. Gene transcript differences between patients with CRS and controls were compared and correlated with disease severity metrics. Immunohistochemical analyses of CCL19, CCR7, and CCRL1 were conducted to compare differences in protein expression between cohorts. A subgroup analysis was performed to compare transcriptional and protein expression difference between patients with (CRSwNP) and without (CRSsNP) nasal polyps and controls.
Results
Thirty-eight subjects (control group, n=7; CRS group, n=31) were included in this study.
CCRL1
(
p
=0.0093) and
CCR7
(
p
=0.017) levels were significantly elevated in CRS compared to those in controls.
CCL19
(
p
=0.038) and
CCR7
(
p
=0.0097) levels were elevated in CRSwNP and
CCRL1
was elevated in CRSsNP (
p
=0.0004). CCR7 expression was significantly elevated in sinonasal epithelial cells in CRSwNP (
p
=0.04).
CCL19
expression was positively correlated with
TNFA
expression (
p
<0.0002).
CCL19 and CCR7
expression was positively correlated with SNOT-22 and RSDI scores (
p
<0.05).
Conclusion
CCL19 and CCR7 may modulate TNF-α-driven pro-inflammatory signaling and contribute to increased disease severity in CRS. Mechanistic studies are required to further elucidate the role of CCRL1 in CRS.