SHIP-1 Differentially Regulates IgE-induced IL-10 and Antiviral Responses in Human Monocytes

Overview

Journal bioRxiv

Date 2024 Feb 19

PMID 38370636

Authors

Siva Kumar Solleti

Bailey E Matthews

Regina K Rowe

Affiliations

Soon will be listed here.

Abstract

IgE-mediated stimulation of monocytes regulates multiple cellular functions including cellular maturation, cytokine release, antiviral responses, and T cell priming and differentiation. The high affinity IgE receptor, FcεRI, is closely linked to serum IgE levels and atopic disease. The signaling molecules which regulate effector functions of this receptor have been well studied in mast cells and basophils, however, less is known about the signaling components, regulatory molecules, and mechanisms downstream of receptor activation in monocytes. This study sought to identify regulators of IgE-mediated cytokine release in human monocytes. SHIP-1 was identified as a negative regulator of IgE-induced IL-10 production. It was also determined that IgE-mediated stimulation and SHIP-1 inhibition decreased antiviral IP-10 production after liposomal poly(I:C) stimulation, indicating differential regulation by SHIP-1 in IgE-driven and antiviral response pathways. Both SHIP-1 and NF-κB were activated following IgE-mediated stimulation of primary monocytes, and NF-κB activation was related to both SHIP-1 and FcεRIα expression levels in monocytes. To our knowledge this is the first study to identify a role for SHIP-1 in regulating IgE-driven responses and antiviral responses in human monocytes. Given the importance of monocytes in inflammation and immune responses, a better understanding of the signaling and regulatory mechanisms downstream of FcεRI receptor could lead to new therapeutic targets in allergic disease.

References

Li H, Wang H, Sokulsky L, Liu S, Yang R, Liu X . Single-cell transcriptomic analysis reveals key immune cell phenotypes in the lungs of patients with asthma exacerbation. J Allergy Clin Immunol. 2020; 147(3):941-954. DOI: 10.1016/j.jaci.2020.09.032. View

Borkowski T, Jouvin M, Lin S, Kinet J . Minimal requirements for IgE-mediated regulation of surface Fc epsilon RI. J Immunol. 2001; 167(3):1290-6. DOI: 10.4049/jimmunol.167.3.1290. View

Pyle D, Yang V, Gruchalla R, Farrar J, Gill M . IgE cross-linking critically impairs human monocyte function by blocking phagocytosis. J Allergy Clin Immunol. 2013; 131(2):491-500.e1-5. PMC: 3564054. DOI: 10.1016/j.jaci.2012.11.037. View

Roth K, Chen W, Lin T . Positive and negative regulatory mechanisms in high-affinity IgE receptor-mediated mast cell activation. Arch Immunol Ther Exp (Warsz). 2008; 56(6):385-99. DOI: 10.1007/s00005-008-0041-2. View

Rowe R, Pyle D, Tomlinson A, Lv T, Hu Z, Gill M . IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven T1 differentiation. J Allergy Clin Immunol. 2017; 140(1):294-298.e8. PMC: 5794014. DOI: 10.1016/j.jaci.2016.11.035. View

Eguiluz-Gracia I, Bosco A, Dollner R, Melum G, Lexberg M, Jones A . Rapid recruitment of CD14(+) monocytes in experimentally induced allergic rhinitis in human subjects. J Allergy Clin Immunol. 2016; 137(6):1872-1881.e12. DOI: 10.1016/j.jaci.2015.11.025. View

Yeoh W, Krebs P . SHIP1 and its role for innate immune regulation-Novel targets for immunotherapy. Eur J Immunol. 2023; 53(12):e2350446. DOI: 10.1002/eji.202350446. View

Tebo J, Kim H, Gao J, Armstrong D, Hamilton T . Interleukin-10 suppresses IP-10 gene transcription by inhibiting the production of class I interferon. Blood. 1998; 92(12):4742-9. View

Gibbs B, Rathling A, Zillikens D, Huber M, Haas H . Initial Fc epsilon RI-mediated signal strength plays a key role in regulating basophil signaling and deactivation. J Allergy Clin Immunol. 2006; 118(5):1060-7. DOI: 10.1016/j.jaci.2006.07.022. View

10.

Gill M, Bajwa G, George T, Dong C, Dougherty I, Jiang N . Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells. J Immunol. 2010; 184(11):5999-6006. PMC: 4820019. DOI: 10.4049/jimmunol.0901194. View

11.

Lin S, Cicala C, Scharenberg A, Kinet J . The Fc(epsilon)RIbeta subunit functions as an amplifier of Fc(epsilon)RIgamma-mediated cell activation signals. Cell. 1996; 85(7):985-95. DOI: 10.1016/s0092-8674(00)81300-8. View

12.

Gilfillan A, Rivera J . The tyrosine kinase network regulating mast cell activation. Immunol Rev. 2009; 228(1):149-69. PMC: 2669301. DOI: 10.1111/j.1600-065X.2008.00742.x. View

13.

Le T, Tversky J, Chichester K, Bieneman A, Huang S, Wood R . Interferons modulate Fc epsilon RI-dependent production of autoregulatory IL-10 by circulating human monocytoid dendritic cells. J Allergy Clin Immunol. 2008; 123(1):217-23. PMC: 2674243. DOI: 10.1016/j.jaci.2008.09.013. View

14.

Conde C, Rambout X, Lebrun M, Lecat A, Di Valentin E, Dequiedt F . The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-κB activation by disturbing the interaction of XIAP with RIP2. PLoS One. 2012; 7(7):e41005. PMC: 3398883. DOI: 10.1371/journal.pone.0041005. View

15.

Kalesnikoff J, Baur N, Leitges M, Hughes M, Damen J, Huber M . SHIP negatively regulates IgE + antigen-induced IL-6 production in mast cells by inhibiting NF-kappa B activity. J Immunol. 2002; 168(9):4737-46. DOI: 10.4049/jimmunol.168.9.4737. View

16.

Rowe R, Pyle D, Farrar J, Gill M . IgE-mediated regulation of IL-10 and type I IFN enhances rhinovirus-induced Th2 differentiation by primary human monocytes. Eur J Immunol. 2020; 50(10):1550-1559. DOI: 10.1002/eji.201948396. View

17.

Sly L, Hamilton M, Kuroda E, Ho V, Antignano F, Omeis S . SHIP prevents lipopolysaccharide from triggering an antiviral response in mice. Blood. 2009; 113(13):2945-54. PMC: 2662641. DOI: 10.1182/blood-2008-06-166082. View

18.

Costello P, Turner M, Walters A, Cunningham C, Bauer P, Downward J . Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells. Oncogene. 1996; 13(12):2595-605. View

19.

Schroeder J, Bieneman A, Xiao H, Chichester K, Vasagar K, Saini S . TLR9- and FcepsilonRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression. J Immunol. 2005; 175(9):5724-31. DOI: 10.4049/jimmunol.175.9.5724. View

20.

Solleti S, Srisuma S, Bhattacharya S, Rangel-Moreno J, Bijli K, Randall T . Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation. FASEB J. 2016; 30(7):2615-26. PMC: 6137455. DOI: 10.1096/fj.201500159R. View