Basophils from allergic patients are neither hyperresponsive to activation signals nor hyporesponsive to inhibition signals

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:142

Article

Cassard, Lydie^1,2,7  Sperber, Katia^1,2,8  Buivan, Tan-Phut^1,2,9  Cotillard, Aurelie³  Bourdet-Sicard, Raphaelle⁴  Albert, Matthew L.^1,2,10  Mottez, Estelle^1,2  Laurent, Jerome^5,11  Guinnepain, Marie-Therese^5,12  Daeron, Marc^1,6,13,14 

[1] Inst Pasteur, Ctr Immunol Humaine, Dept Immunol, Paris, France

[2] INSERM, Inst Pasteur, UMS 20, Paris, France

[3] Soladis, Lyon, France

[4] Danone Res, Palaiseau, France

[5] Inst Pasteur, Ctr Med, Paris, France

[6] Aix Marseille Univ, CNRS, Ctr Immunol Marseille Luminy, INSERM, Marseille, France

[7] Gustave Roussy Canc Campus, Lab Immunomonitoring Oncol, Villejuif, France

[8] Lab Virbac, Preclin & Clin Unit, Carros, France

[9] Inst Pasteur, Ctr Rech Translat, Paris, France

[10] Inst Pasteur, Dept Immunol, Inserm U818, Unite Immunobiol Cellules Dendrit, Paris, France

[11] Hop Europeen Georges Pompidou, Serv Immunol, Paris, France

[12] Hop Foch, Suresnes, France

[13] Inst Pasteur, Direct Dev, Grant Off, Paris, France

[14] Ctr Immunol Marseille Luminy, Marseille, France

关键词: Anaphylaxis;    asthma;    atopic dermatitis;    basophil activation;    chronic urticaria;    Fc epsilon RI;    Fc gamma RIIB;    lactobacilli;    negative regulation;    rhinitis;   

DOI  :  10.1016/j.jaci.2017.11.053

来源: Elsevier

【 摘 要 】

Background: Basophil activation contributes to inflammatory reactions, especially in allergy. It is controlled, both positively and negatively, by several mechanisms. High-affinity IgE receptors (Fc epsilon RI) generate a mixture of activation and inhibition signals when aggregated, the ratio of which depends on the concentration of allergen recognized by receptor-bound IgE. Low-affinity IgG receptors (Fc gamma RIIA/B) generate inhibition signals when coengaged with Fc epsilon RI by allergen-antibody immune complexes. Commensal and probiotic bacteria, such as Lactobacillus paracasei, generate inhibition signals through still unclear mechanisms. Objective: We sought to investigate whether mechanisms that control, both positively and negatively, basophil activation, which were unraveled and studied in basophils from healthy donors, are functional in allergic patients. Methods: Fc epsilon RI and Fc gamma RIIA/B expression, Fc epsilon RI-dependent activation, FceRI-dependent inhibition, and Fc gamma RIIB-dependent inhibition were examined in blood basophils incubated overnight with or without L paracasei and challenged under 10 experimental conditions. Basophils from healthy donors were compared with basophils from patients who consulted an allergology outpatient clinic over a period of 3 months with respiratory allergy, anaphylaxis antecedents, chronic urticaria, and/or atopic dermatitis. Results: Patients' basophils expressed neither more Fc epsilon RI nor less Fc gamma RIIB than basophils from healthy donors. They were neither hyperreactive to positive regulation nor hyporeactive to negative regulation, irrespective of the receptors or mechanisms involved and the allergic manifestations of the patients. Conclusion: Regulatory mechanisms that control basophil activation are fully functional in allergic patients. Intrinsic defects in these mechanisms do not explain allergic manifestations. Based on these mechanisms, immune checkpoint modifiers can be developed as novel therapeutic tools for allergy.

【 授权许可】

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