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. 2025 Feb;55(2):e202451065.
doi: 10.1002/eji.202451065. Epub 2024 Dec 12.

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

Siva Kumar Solleti  1 , Bailey E Matthews  1 , Jingyi Wu  2 , Regina K Rowe  1
Affiliations

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

Siva Kumar Solleti et al. Eur J Immunol. 2025 Feb.

Abstract

IgE-mediated stimulation of monocytes regulates multiple cellular functions including cellular maturation, cytokine release, antiviral responses, and T-cell differentiation. Expression of the high-affinity IgE receptor, FcεRI, is closely linked to serum IgE levels and atopic disease. The signaling molecules regulating FcεRI effector functions have been well studied in mast cells and basophils; however, less is known about the signaling and regulatory mechanisms 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. SHIP-1 and NF-κB were activated following IgE-mediated stimulation of monocytes, and NF-κB activation was related to both SHIP-1 and FcεRIα cellular expression levels. To our knowledge, this is the first study to identify a role for SHIP-1 in regulating IgE-mediated 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 the FcεRI receptor could lead to new therapeutic targets in allergic disease.

Keywords: IL‐10; IP‐10; IgE; SHIP‐1; monocyte.

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