The FcεRIβ homologue, MS4A4A, promotes FcεRI signal transduction and store-operated Ca2+ entry in human mast cells

Arthur, Greer; Ehrhardt-Humbert, Lauren; Snider, Douglas B.; Jania, Corey M.; Tilley, Stephen L.; Metcalfe, Dean D.; Cruse, Glenn

doi:10.1016/j.cellsig.2020.109617

Cited by 12 publications

(24 citation statements)

References 52 publications

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“…A recent report showed that downregulation of MS4A4A via short hairpin (sh)RNA knockdown (KD) in the human mast cell line LAD-2 correlated with reduced Ca 2+ influx upon IgE crosslinking, arguing for a potential role of MS4A4A in regulating store-operated Ca 2+ entry, which, in mast cells, is mainly controlled by the Ca 2+ channel pore-forming unit Orai1 [53]. and Orai1 KD had no additive effect; therefore, the authors concluded that MS4A4A likely regulates Orai1 activity as a consequence of Ca 2+ influx [53]. Given that the MS4A4A impact on Ca 2+ flux in mast cells appears to be indirect, this rules out the possibility that MS4A4A works as a Ca 2+ channel (Figure 2).…”

Section: Box 2 Comparison Of Ms4a Proteins and Tetraspaninsmentioning

confidence: 99%

“…By regulating ion exchange and modulating the signaling cascade of partnering immunoreceptors, MS4A proteins can work as amplifiers for the activation of immune cells they are expressed on, contributing to determining the strength of immune reactions. Human MS4A1, MS4A2, and MS4A4A and human and murine TMEM176 have been associated with the regulation of ion exchange[35,39,53,61]. Human MS4A2, MS4A4A, together with murine Ms4a6d, are also involved in the modulation of the biological functions of other immunoreceptor, such as FcεRI, Dectin-1, and V-set and immunoglobulin domaincontaining 4 (Vsig4)[8,10,38].…”

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confidence: 99%

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The tetraspan MS4A family in homeostasis, immunity, and disease

Mattiola

Mantovani

Locati

2021

Trends in Immunology

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Section: Box 2 Comparison Of Ms4a Proteins and Tetraspaninsmentioning

confidence: 99%

mentioning

confidence: 99%

The tetraspan MS4A family in homeostasis, immunity, and disease

Mattiola

Mantovani

Locati

2021

Trends in Immunology

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“…MS4A4A is expressed by Mϕs 8,9 and further induced by M2‐like stimuli 9,23,24 . Additionally, MS4A4A was also reported to be expressed by mast cells, playing an important role in the regulation of trafficking, signaling, and recycling of tyrosine kinase stem cell factor receptor (KIT), 25 and in mediating FcƐRI signaling 26 …”

Section: Introductionmentioning

confidence: 99%

Differential expression and regulation of MS4A family members in myeloid cells in physiological and pathological conditions

Silva-Gomes

Mapelli

Boutet

et al. 2021

Journal of Leukocyte Biology

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The MS4A gene family encodes 18 tetraspanin-like proteins, most of which with unknown function. MS4A1 (CD20), MS4A2 (FcεRIβ), MS4A3 (HTm4), and MS4A4A play important roles in immunity, whereas expression and function of other members of the family are unknown. The present investigation was designed to obtain an expression fingerprint of MS4A family members, using bioinformatics analysis of public databases, RT-PCR, and protein analysis when possible. MS4A3, MS4A4A, MS4A4E, MS4A6A, MS4A7, and MS4A14 were expressed by myeloid cells. MS4A6A and MS4A14 were expressed in circulating monocytes and decreased during monocyte-to-Mϕ

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“…However, in the case of C5a, β-arrestin recruitment is not thought to impact on ERK1/2 signaling ( 64 ). Indeed, there are multiple levels at which MC degranulation, calcium flux and ERK1/2 might be modulated in MCs ( 69 ). IL-33 amplifies the observed differences and translates them in distinct functional properties such as the increase in MCP-1 secretion induced by C5a.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-33 Amplifies Human Mast Cell Activities Induced by Complement Anaphylatoxins

et al. 2021

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Both, aberrant mast cell responses and complement activation contribute to allergic diseases. Since mast cells are highly responsive to C3a and C5a, while Interleukin-33 (IL-33) is a potent mast cell activator, we hypothesized that IL-33 critically regulates mast cell responses to complement anaphylatoxins. We sought to understand whether C3a and C5a differentially activate primary human mast cells, and probe whether IL-33 regulates C3a/C5a-induced mast cell activities. Primary human mast cells were generated from peripheral blood precursors or isolated from healthy human lung tissue, and mast cell complement receptor expression, degranulation, mediator release, phosphorylation patterns, and calcium flux were assessed. Human mast cells of distinct origin express constitutively higher levels of C3aR1 than C5aR1, and both receptors are downregulated by anaphylatoxins. While C3a is a potent mast cell degranulation inducer, C5a is a weaker secretagogue with more delayed effects. Importantly, IL-33 potently enhances the human mast cell reactivity to C3a and C5a (degranulation, cytokine and chemokine release), independent of changes in C3a or C5a receptor expression or the level of Ca2+ influx. Instead, this reflects differential dynamics of intracellular signaling such as ERK1/2 phosphorylation. Since primary human mast cells respond differentially to anaphylatoxin stimulation, and that IL-33 is a key regulator of mast cell responses to complement anaphylatoxins, this is likely to aggravate Th2 immune responses. This newly identified cross-regulation may be important for controlling exacerbated complement- and mast cell-dependent Th2 responses and thus provides an additional rationale for targeting anti-IL33 therapeutically in allergic diseases.

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The FcεRIβ homologue, MS4A4A, promotes FcεRI signal transduction and store-operated Ca2+ entry in human mast cells

Cited by 12 publications

References 52 publications

The tetraspan MS4A family in homeostasis, immunity, and disease

The tetraspan MS4A family in homeostasis, immunity, and disease

Differential expression and regulation of MS4A family members in myeloid cells in physiological and pathological conditions

Interleukin-33 Amplifies Human Mast Cell Activities Induced by Complement Anaphylatoxins

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