The SP‐TLR axis, which locally primes the nasal mucosa, is impeded in patients with allergic rhinitis

Abstract

Background Substance P (SP) and toll‐like receptors (TLRs) contribute to airway disease, particularly during viral infection. We recently demonstrated that SP can act as an initial response to viral stimuli in the upper airway by upregulating TLRs in the nasal epithelia (the SP‐TLR axis). Patients with allergic rhinitis (AR) suffer from prolonged airway infections. The aim of the present study was to examine if patients with AR exhibit a disturbance in the SP‐TLR axis. Method Human nasal biopsies and human nasal epithelial cells (HNEC) from healthy volunteers and patients with AR were cultured in the presence of SP. Epithelial expression of TLR4, neutral endopeptidase (NEP) and neurokinin 1 (NK1) were evaluated with flow cytometry and/or quantitative polymerase chain reaction after 30 min to 24 h. The effect of SP on nasal lipopolysaccharide‐induced interleukin‐8 (IL‐8) release was investigated. Results SP stimulation of tissue from healthy volunteers resulted in a transient increase of the TLR4 expression, whereas stimulation of AR patient‐derived material led to a delayed and prolonged upregulation of TLR4. NEP expression in HNEC was lower in AR than healthy controls whereas NK1 receptor expression was increased. SP pretreatment increased TLR4‐dependent IL‐8 expression in healthy controls, but not in AR. Conclusions SP‐induced regulation of TLR4 in the human nasal mucosa is disturbed in AR. An altered SP‐mediated innate immune response may contribute to the dysfunctional and often prolonged responses to infection in AR.

Pathogenesis of chronic rhinosinusitis with nasal polyp and a prominent T2 endotype

“…Toll-like receptors (TLRs) contribute to airway disease and their expression level and function are altered in response to viral and bacterial particles [ 50 ]. TLR2 and TLR4 are shown to be increased in CRSwNP epithelial cells compared to normal nasal epithelial cells [ 47 ].…”

Neuroimmune communication in allergic rhinitis

“…In addition to its effect on MCs, recent studies have demonstrated that a burst of neuronal and epithelial SP serves as an initial defensive response in the nose ( 66 ). A recent study on patients with AR demonstrated that the SP-Toll-like receptor axis is impaired with delayed and prolonged upregulation of TLR4, which contributes to the more severe and persistent responses to infection in AR ( 78 ). This may aggravate nasal symptoms of AR, especially when encountered with infections.…”

The Assessment of TLR1 Gene Polymorphism Association with the Risk of Allergic Rhinitis in the Chinese Han Population from Northern China

“…It has been reported that TLRs are involved in the pathogenesis of AR. 12,13 Renkonen et al have found the protein expression levels of TLR1 and TLR6 are down-regulated in the allergic group after allergen stimulation. 14 Another study has also revealed that the expression levels of TLR2 and TLR4 are increased in patients with AR compared with controls.…”