Regulation of neutrophils in type 2 immune responses

Heeb, Lukas E. M.; Egholm, Cecilie; Impellizzieri, Daniela; Ridder, Frederike; Boyman, Onur

doi:10.1016/j.coi.2018.06.009

Cited by 28 publications

(35 citation statements)

References 76 publications

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“…IL-4 has been widely studied in relation to its effect on lymphoid cells, centrally involved in T helper cell differentiation, B cell class switch (52,53), as well as effects on nonimmune stromal cells (54). An emerging field related to IL-4R signaling in neutrophils is broadening the implications under conditions with increased IL-4 and IL-13 levels, such as allergic reactions and parasitic infections, but also related to therapeutic interventions affecting this pathway (55,56). For example, an interesting connection between the increased susceptibility to skin infections in patients with the TH2 centric disease atopic dermatitis and the suppression of neutrophil migration by IL-4R signaling has been proposed (29,34).…”

Section: Discussionmentioning

confidence: 99%

IL-4 controls activated neutrophil FcγR2b expression and migration into inflamed joints

Panda

Wigerblad

Jiang

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Neutrophils are the most abundant immune cells found in actively inflamed joints of patients with rheumatoid arthritis (RA), and most animal models for RA depend on neutrophils for the induction of joint inflammation. Exogenous IL-4 and IL-13 protect mice from antibody-mediated joint inflammation, although the mechanism is not understood. Neutrophils display a very strong basal expression of STAT6, which is responsible for signaling following exposure to IL-4 and IL-13. Still, the role of IL-4 and IL-13 in neutrophil biology has not been well studied. This can be explained by the low neutrophil surface expression of the IL-4 receptor α-chain (IL-4Rα), essential for IL-4– and IL-13–induced STAT6 signaling. Here we identify that colony stimulating factor 3 (CSF3), released during acute inflammation, mediates potent STAT3-dependent neutrophil IL-4Rα up-regulation during sterile inflammatory conditions. We further demonstrate that IL-4 limits neutrophil migration to inflamed joints, and that CSF3 combined with IL-4 or IL-13 results in a prominent neutrophil up-regulation of the inhibitory Fcγ receptor (FcγR2b). Taking these data together, we demonstrate that the IL-4 and CSF3 pathways are linked and play important roles in regulating proinflammatory neutrophil behavior.

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Section: Discussionmentioning

confidence: 99%

IL-4 controls activated neutrophil FcγR2b expression and migration into inflamed joints

Panda

Wigerblad

Jiang

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…168,169 Rare, however significant side effects 170 and the not yet completely understood effects of IL-4 on innate immune function warrant further investigation. 171,172 Studies investigating the role of TSLP and IL-25 in the context of food allergy are limited, and recent data on the topic are still derived from rodent in vivo and in vitro models. 15,85 Currently, there are trials of biologics targeting TSLP in asthma (NCT02698501), and in combination with cat immunotherapy (NCT02237196), but not food allergies.…”

Section: Antig En -Uns Pecific and Additive A Pproache Smentioning

confidence: 99%

Recent developments and highlights in food allergy

Eiwegger

Hung

Diego

et al. 2019

Allergy

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The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features.Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development.Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit.More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that. K E Y W O R D Sallergy treatment, biologics, food allergy, immune tolerance, immunotherapy | 2357 EIWEGGER Et al.

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“…However, the regulation and role of neutrophils during type 2 (or T H 2 cell) immune responses remain ill-defined. [6][7][8][9] Type 2 immune responses evolved to protect the host against large extracellular parasitic helminths, venoms, and toxins by strengthening epithelial barrier defenses and stimulating different immune cell mechanisms. 10,11 Many of these effects are initiated, driven, and maintained by the actions of type 2 cytokines, most notably IL-4 and IL-13, which signal through heterodimeric IL-4 receptors (IL-4Rs).…”

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confidence: 99%