Journal of Inflammation Research (May 2024)

Chemokine CCL19 and Its Receptors CCR7 and CCRL1 in Chronic Rhinosinusitis

  • Mahomva CR,
  • Smith KA,
  • Minkah PAB,
  • Witt BL,
  • Oakley GM,
  • Orlandi RR,
  • Alt JA,
  • Pulsipher A

Journal volume & issue
Vol. Volume 17
pp. 2991 – 3002

Abstract

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Chengetai R Mahomva,1,* Kristine A Smith,1,* Prince AB Minkah,2 Benjamin L Witt,3 Gretchen M Oakley,1 Richard R Orlandi,1 Jeremiah A Alt,1,2,4 Abigail Pulsipher1,2,4 1Department of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA; 2Department of Molecular Pharmaceutics, University of Utah College of Pharmacy, Salt Lake City, UT, USA; 3Cytopathology Section, University of Utah School of Medicine, Salt Lake City, UT, USA; 4Utah Center for Nanomedicine, University of Utah College of Pharmacy, Salt Lake City, UT, USA*These authors contributed equally to this workCorrespondence: Abigail Pulsipher, University of Utah School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 36 South Wasatch Drive, Salt Lake City, UT, 84112, USA, Tel +1 4342493268, Fax +1 8015855744, Email [email protected]: 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.Keywords: chronic rhinosinusitis with nasal polyps, chemokines, cytokines, gene expression, protein expression

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