The immunomodulatory potentials of interleukin‐27 in airway allergies

Jafarzadeh, Abdollah; Nemati, Maryam; Jafarzadeh, Sara; Chauhan, Prashant; Saha, Bhaskar

doi:10.1111/sji.12959

Cited by 11 publications

(9 citation statements)

References 126 publications

(243 reference statements)

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“…The effect of IL-27 in airway allergies depends on the balance of its signaling pathways on different target cells of innate immunity and adaptive immunity and the stage of allergic response. 23 Many inconsistencies exist when evaluating its role in allergic airway disease, as IL-27 may have pro-inflammatory and attenuating effects. Nevertheless, it is known that tolerance induction during AIT is supported by dendritic cells influencing naïve T-cells with a cocktail of IL-10, IL-12, and IL-27 to either provoke Th1 deviation or induction of regulatory T-cells (Tregs)- both promoting a Th1 dominant milieu.…”

Section: Discussionmentioning

confidence: 99%

Plasma-derived extracellular vesicles discriminate type-1 allergy subjects from non-allergic controls

Wagner

Eberhardt

Vera

et al. 2021

World Allergy Organization Journal

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Background Allergies are on the rise globally, with an enormous impact on affected individuals’ quality of life as well as health care resources. They cause a wide range of symptoms, from slightly inconvenient to potentially fatal immune reactions. While allergies have been described and classified phenomenologically, there is an unmet need for easily accessible biomarkers to stratify the severity of clinical symptoms. Furthermore, biomarkers marking the success of specific immunotherapy are urgently needed. Objectives Plasma extracellular vesicles (pEV) play a role in coordinating the immune response and may be useful future biomarkers. A pilot study on differences in pEV content was carried out between patients with type I allergy, suffering from rhinoconjunctivitis with or without asthma, and voluntary non-allergic donors. Methods We examined pEV from 38 individuals (22 patients with allergies and 16 controls) for 38 chemokines, cytokines, and soluble factors using high-throughput data mining approaches. Results Patients with allergies had a distinct biomarker pattern, with 7 upregulated (TNF-alpha, IL-4, IL-5, IL-6, IL-17F, CCL2, and CCL17) and 3 downregulated immune mediators (IL-11, IL-27, and CCL20) in pEV compared to controls. This reduced set of 10 factors was able to discriminate controls and allergic patients better than the total array. Conclusions The content of pEV showed potential as a target for biomarker research in allergies. Plasma EV, which are readily measurable via blood test, may come to play an important role in allergy diagnosis. In this proof-of-principle study, it could be shown that pEV's discriminate patients with allergies from controls. Further studies investigating whether the content of pEVs may predict the severity of allergic symptoms or even the induction of tolerance to allergens are needed.

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Section: Discussionmentioning

confidence: 99%

Plasma-derived extracellular vesicles discriminate type-1 allergy subjects from non-allergic controls

Wagner

Eberhardt

Vera

et al. 2021

World Allergy Organization Journal

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“…3D ). Both Interferon lambda 1 and IL-27 are known to promote the induction of T helper (T H )1 cells during naive T cell differentiation by either stimulating interferon response genes or inflammatory cytokines, like IL-6 [ 43 , 44 ]. These two altered DEGs therefore imply a role for α2-3sia dendrimers in diverting T H 1 differentiation.…”

Section: Resultsmentioning

confidence: 99%

α2-3 Sialic acid binding and uptake by human monocyte-derived dendritic cells alters metabolism and cytokine release and initiates tolerizing T cell programming

Lubbers

Gorki

et al. 2021

Immunotherapy Advances

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Dendritic cells (DCs) are key in the initiation of the adaptive T cell responses to tailor adequate immunity that corresponds to the type of pathogen encountered. Oppositely, DCs control the resolution phase of inflammation and are able to induce tolerance after receiving anti-inflammatory cytokines or upon encounter of self-associated molecular patterns, such as α2-3 linked sialic acid(α2-3sia). We here investigated whether α2-3sia, that bind immune inhibitory Siglec receptors, would alter signaling and reprogramming of LPS-stimulated human monocyte-derived DCs(moDCs). Transcriptomic analysis of moDCs stimulated with α2-3sia conjugated dendrimers revealed differentially expressed genes related to metabolic pathways, cytokines and T cell differentiation. An increase in genes involved in ATPase regulator activity, oxidoreductase activity and glycogen metabolic processes was detected. Metabolic extracellular flux analysis confirmed a more energetic moDC phenotype upon α2-3sia binding as evidenced by an increase in both glycolysis and mitochondrial oxidative phosphorylation. TH1 differentiation promoting genes IFNL and IL27, were significantly downregulated in the presence of α2-3sia. Functional assays confirmed that α2-3sia binding to moDCs induced phosphorylation of Siglec-9, reduced production of inflammatory cytokines IL-12 and IL-6, and increased IL-10. Surprisingly, α2-3sia-differentiated moDCs promoted FoxP3 +CD25 +/-CD127 - regulatory T cell differentiation and decreased FoxP3 -CD25 -CD127 - effector T cell proliferation. In conclusion, we demonstrate that α2-3sia binding to moDCs, phosphorylates Siglec-9, alters metabolic pathways, cytokine signaling and T cell differentiation processes in moDCs and promotes regulatory T cells. The sialic acid-Siglec axis on DCs is therefore, a novel target to induce tolerance and to explore for immunotherapeutic interventions aimed to restore inflammatory processes.

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“…Some studies have reported that IL-27 levels were decreased in allergic diseases [ 25 , 26 , 32 ]. Allergic rhinitis, asthma, and FPIES are T cell-related hypersensitivity disorders [33] , [34] , [35] . However, unlike allergic rhinitis and asthma, which are characterized by elevated IgE, many patients with FPIES may have low levels of IgE [35] .…”

Section: Discussionmentioning

confidence: 99%

IL-27 as a potential biomarker for distinguishing between necrotising enterocolitis and highly suspected early-onset food protein-induced enterocolitis syndrome with abdominal gas signs

Liu

Zhong

et al. 2021

eBioMedicine

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Background: The initial clinical manifestations and abdominal imaging findings of neonates with necrotising enterocolitis (NEC) and food protein-induced enterocolitis syndrome (FPIES) are sometimes similar; however, their prognosis and therapies are different. We aimed to evaluate the utility of interleukin (IL)-27 as a differentiation marker between NEC and highly suspected early onset (HSEO)-FPIES. Methods: All samples used in this study were obtained from the neonatal diagnosis centre of Children's Hospital of Chongqing Medical University. In the case-control study, neonates with NEC (n = 13), HSEO-FPIES (n = 9), and jaundice (control, n = 8) were enroled to determine the serum IL-27 levels using commercial enzyme-linked immunosorbent assay (ELISA) kits. In the validation cohort study, the NEC (n = 87), HSEO-FPIES (n = 62), and jaundice (control, n = 54) groups were included to analyse the diagnostic efficiency of IL-27 for discriminating between NEC and HSEO-FPIES using a receiver operating characteristic (ROC) curve. Findings: In the case-control study, IL-27 levels were higher in the NEC group than in the HSEO-FPIES group (p = 0¢005). In the cohort study, the area under the ROC curve (AUC) of IL-27 for differentiating NEC from HSEO-FPIES was 0¢878, which was higher than the AUCs of IL-6 (0¢761), C-reactive protein (0¢800), white blood cell count (0¢637), neutrophils (0¢765), lymphocytes (0¢782), neutrophil to lymphocyte ratio (0¢781), and platelet count (0¢729). Interpretation: Serum IL-27 is a novel biomarker that may potentially discriminate NEC from HSEO-FPIES in neonates.

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The immunomodulatory potentials of interleukin‐27 in airway allergies

Cited by 11 publications

References 126 publications

Plasma-derived extracellular vesicles discriminate type-1 allergy subjects from non-allergic controls

Plasma-derived extracellular vesicles discriminate type-1 allergy subjects from non-allergic controls

α2-3 Sialic acid binding and uptake by human monocyte-derived dendritic cells alters metabolism and cytokine release and initiates tolerizing T cell programming

IL-27 as a potential biomarker for distinguishing between necrotising enterocolitis and highly suspected early-onset food protein-induced enterocolitis syndrome with abdominal gas signs

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