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Review
. 2022 Sep 14:13:937120.
doi: 10.3389/fimmu.2022.937120. eCollection 2022.

Utilizing mast cells in a positive manner to overcome inflammatory and allergic diseases

Zhongwei Zhang  1 , Peter B Ernst  2   3   4 , Hiroshi Kiyono  4   5   6   7   8   9   10 , Yosuke Kurashima  1   6   9   10   11   12
Affiliations
Review

Utilizing mast cells in a positive manner to overcome inflammatory and allergic diseases

Zhongwei Zhang et al. Front Immunol. .

Abstract

Mast cells (MCs) are immune cells widely distributed in the body, accompanied by diverse phenotypes and functions. Committed mast cell precursors (MCPs) leave the bone marrow and enter the blood circulation, homing to peripheral sites under the control of various molecules from different microenvironments, where they eventually differentiate and mature. Partly attributable to the unique maturation mechanism, MCs display high functional heterogeneity and potentially plastic phenotypes. High plasticity also means that MCs can exhibit different subtypes to cope with different microenvironments, which we call "the peripheral immune education system". Under the peripheral immune education system, MCs showed a new character from previous cognition in some cases, namely regulation of allergy and inflammation. In this review, we focus on the mucosal tissues, such as the gastrointestinal tract, to gain insights into the mechanism underlying the migration of MCs to the gut or other organs and their heterogeneity, which is driven by different microenvironments. In particular, the immunosuppressive properties of MCs let us consider that positively utilizing MCs may be a new way to overcome inflammatory and allergic disorders.

Keywords: allergy; heterogeneity; inflammation; mast cells; tolerance.

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Conflict of interest statement

HK is director and founder of HanaVax Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Assembly of MCs in the gut. The MCPs leave the hematopoietic tissue, enter the blood stream, migrate and colonize the target tissue. With c-kit, CXCR2, and integrin α4β7 on the cell surface, MCPs bind to MAdCAM-1 and VCAM1 on the vascular endothelial cells, thereby crossing the vascular endothelium and colonizing the intestinal mucosa and submucosa, where they mature. In addition, transcription factor (dendritic cell-derived T-bet), Lipid mediator (sphingosine 1-phosphate), and some intestinal microbiota affect the homing of MCs to the gut.
Figure 2
Figure 2
Heterogeneity of MCs. MCs mature uniquely, developing them more susceptible to the tissue homeostasis of the peripheral tissue microenvironment, and thus exhibit different subtypes and secrete different mediators to achieve different functions.
Figure 3
Figure 3
Regulatory properties of MCs in the immunotherapy. OIT treatment for food allergy induces desensitization of MCs with the low expression of Th2 cytokines and induces expression of IFN-γ. Desensitized MCs also synthesize IL-2 and IL-10. MC-derived IL-2 and amphiregulin promote proliferation and enhancement of the function of Tregs. Activated Tregs release IL-10 and TGF-β1, and the OX40 on their surface binds to OX40L from MCs, which inhibits the expression of FcϵRI on MCs and the release of TNF-α and IL-13, thereby inhibiting the Th2 responses.
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