Novel cooperation between <scp>CX</scp>3<scp>CL</scp>1 and <scp>CCL</scp>26 inducing <scp>NK</scp> cell chemotaxis via <scp>CX</scp>3<scp>CR</scp>1: a possible mechanism for <scp>NK</scp> cell infiltration of the allergic nasal tissue

El-Shazly, A. A.; Doloriert, H. C.; Bisig, Bettina; Lefèbvre, Philippe; Delvenne, Philippe; Jacobs, Nathalie

doi:10.1111/cea.12022

Cited by 41 publications

(38 citation statements)

References 40 publications

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Section: Opinion Articlementioning

confidence: 79%

“…We also showed that allergen challenge upregulates the function of CX3CR1 in peripheral blood NK cells and that NK cell infiltrated the epithelial layers of nasal tissue only in chronic rhinosinusitis with allergy (ACRS) patients and not in the chronic rhinosinusitis without allergy (NACRS) patients or controls [7]. This migration could be mediated by CX3CL1, since fractalkine was able to induce NK cytoskeleton changes and F-actin reorganization as well as chemotaxis in microchemotaxis chambers [7].This interesting predominance of CX3CL1/CX3CR1 towards T H2 immunological response in the inflamed nose alerted us to further study fractalkine expression by inflammatory cells infiltrating the inflamed nasal tissue in allergic and non-allergic inflammation. After obtaining the approval of our hospital ethics committee, a total of 28 nasal biopsies from patients operated for CRS by endoscopic sinus surgery, were studied by immunohistochemistry.…”

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confidence: 83%

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Fractalkine and Nasal Inflammation

El-Shazly¹

2017

J immuno Biol

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Opinion ArticleChemokines that attract inflammatory cells play a critical role in promoting nasal inflammation and the development of nasal polyps. CX3CL1 that belongs to CX3C chemokine family is expressed as a membrane bound form and under suitable conditions CX3CL1 is cleaved to its soluble form that has been reported to be higher in the plasma of patients with allergic rhinitis (AR) [1]. The specific receptor for CX3CL1 is the CX3CR1 that is expressed on monocytes, NK cells, T cells and mast cells, mediating adhesion and migration of these leukocytes [2][3][4]. Moreover, segmental allergen challenge up-regulates the function of CX3CR1 in peripheral blood CD4 T cells [4].It is surprisingly that only few reports have studied this important pro-inflammatory axis in the upper airway. Danielsen et al. [5] reported CX3CL1 protein detection in nasal polyps. In another study on the gene expression of CX3CL1/CX3CR1, the authors isolated the total RNAs from the nasal mucosa of 20 allergic rhinitis patients to study the cDNA of chemokines and their receptors. They found that CX3CL1/CX3CR1 among other chemokines and their receptors that play important roles in T H2 response, were upregulated in the nasal mucosa of AR patients [6]. We also showed that allergen challenge upregulates the function of CX3CR1 in peripheral blood NK cells and that NK cell infiltrated the epithelial layers of nasal tissue only in chronic rhinosinusitis with allergy (ACRS) patients and not in the chronic rhinosinusitis without allergy (NACRS) patients or controls [7]. This migration could be mediated by CX3CL1, since fractalkine was able to induce NK cytoskeleton changes and F-actin reorganization as well as chemotaxis in microchemotaxis chambers [7].This interesting predominance of CX3CL1/CX3CR1 towards T H2 immunological response in the inflamed nose alerted us to further study fractalkine expression by inflammatory cells infiltrating the inflamed nasal tissue in allergic and non-allergic inflammation. After obtaining the approval of our hospital ethics committee, a total of 28 nasal biopsies from patients operated for CRS by endoscopic sinus surgery, were studied by immunohistochemistry. A total of 28 subjects participated in the study. Out of those, 23 were subjected to endoscopic sinus surgery and their nasal biopsies were obtained by trimming of the middle turbinate as a part of the surgical procedure. As control group, biopsies from the inferior turbinate of patients undergoing partial turbinectomy and did not suffer from either CRS or allergy were obtained (n=5). The 23 patients with CRS were divided into 2 groups: group 1 is 11 patients with NACRS (patients who had no history of allergy and was proven negative to prick skin tests and allergosorbant test (RAST)) while group 2 is 12 patients with ACRS (patients with long history of poorly controlled AR with positive skin tests and RAST to aeroallergens and in whom nasal tissue swelling resulted into obstruction of the ostiomeatal complex and the development of CRS). Interestingly as seen i...

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Section: Opinion Articlementioning

confidence: 79%

mentioning

confidence: 83%

Fractalkine and Nasal Inflammation

El-Shazly¹

2017

J immuno Biol

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“…These findings support the notion that NK cells may have the capacity to regulate the accumulation of eosinophils in sinus tissue as well as blood eosinophilia. El-Shazly et al 37 reported that NK cell infiltration was significantly increased in patients with allergic CRS (patients with a long lasting and poorly controlled allergic rhinitis) without asthma compared with controls, non-allergic CRS, or allergic CRS with asthma patients. Although the two sets of data may not be directly comparable, their results suggest a functional interaction between NK cells and eosinophils in allergic rhinitis patients.…”

Section: Discussionmentioning

confidence: 99%

Natural Killer Cells Regulate Eosinophilic Inflammation in Chronic Rhinosinusitis

Kim

Jang

2015

Journal of Allergy and Clinical Immunology

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Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD 2 , is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD 2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD 2 and its metabolite, but not PGE 2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD 2 -dependent, rather than PGE 2 -dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD 2 , as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS.

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“…There was a higher grade of mucosal inflammation over bone inflammation in both CRS groups. However, there was no correlation between the grade of bone and mucosal inflammation in each studied group [9].At the mucosal level we also showed differences in the magnitude and role of inflammatory cells recruitment to the nasal tissue of CRS patients with or without allergy [10,11]. For example, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in CRS patients with allergic rhinitis and not in CRS patients without allergy or controls.…”

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confidence: 84%

Chronic Rhinosinusitis: Time to Revise the Definition and Phenotypes

El-Shazly¹

2017

Austin J Otolaryngol

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OpinionChronic Rhinosinusitis (CRS) is defined as inflammation of the mucosa lining the paranasal sinuses that lasts more than 12 weeks. Patients with CRS are classified into two subtypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) [1,2]. However, recent evidences indicate that the inflammation reaches beyond the mucosa of the sinus reaching the underlying bones as part of the disease process. Moreover, accumulating evidences indicate the involvement of special molecular events in patients with allergic rhinitis and CRS, pointing to a distinct T H2 pathway driven sinusitis. These findings alert us to consider revising the definition of CRS and to include allergic CRS as a distinct phenotype in the classification of CRS.Patients with CRS are radiologically assessed with Computed Tomography (CT) scans that often reveal areas of increased bone density and irregular thickening of the sinus walls. This could explain the recurrence of the mucosal disease after surgical treatment and may indicate that these osteitic lesions act as the source of the chronic inflammation with worse baseline measures of disease severity and inflammation [3][4][5][6][7]. Other investigators found that the incidence of osteitis reaches 64% in patients with recalcitrant CRS [8].Patients who suffer from allergic rhinitis are also prone to develop CRS. Here, the cytokine profile is biased towards T H2 profile indicating a distinct immunological picture. Our group has shown evidence of osteitis in CRS patients with allergic rhinitis and confirmed the presence of a higher grade osteitis in CRS patients without allergy. There was a higher grade of mucosal inflammation over bone inflammation in both CRS groups. However, there was no correlation between the grade of bone and mucosal inflammation in each studied group [9].At the mucosal level we also showed differences in the magnitude and role of inflammatory cells recruitment to the nasal tissue of CRS patients with or without allergy [10,11]. For example, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in CRS patients with allergic rhinitis and not in CRS patients without allergy or controls. NK cells were also more numerous in the stroma of the nasal tissue from CRS patients with allergic rhinitis compared with CRS patients with no allergy or controls. This is due to CX3CR1-ligand interaction on NK cells, as a result of the T H2 induced immunological response. On the other hand, another study demonstrated a novel neuroimmune axis involving eosinophil recruitment in CRS patients with allergic rhinitis through CRTH2/Vasoactive Intestinal Peptide (VIP) & PGD2 interaction. This further supports a specific type of eosinophilic inflammation in CRS patients with allergic rhinitis. This should not be confused with other distinct phenotypes such as eosinophilic CRS [12].From the above mentioned evidences it is believed that rhinologists should consider the inflammation of CRS as an inflammatory process that can extend beyond the mucous membrane. Th...

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Novel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue

Abstract: Background: Recent data indicated that Natural killer (NK) cells and chemokines could

Cited by 41 publications

References 40 publications

Fractalkine and Nasal Inflammation

Fractalkine and Nasal Inflammation

Natural Killer Cells Regulate Eosinophilic Inflammation in Chronic Rhinosinusitis

Chronic Rhinosinusitis: Time to Revise the Definition and Phenotypes

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