Mast Cells Initiate Type 2 Inflammation through Tryptase Released by MRGPRX2/MRGPRB2 Activation in Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by T helper 2 inflammation as the core pathogenic mechanism. MRGPRX2 plays a key role in nonhistamine allergies and neuroimmune mechanisms in chronic inflammatory dermatitis. However, the role of MRGPRX2 in AD and the development of type 2 inflammation is not yet clear. This study aimed to define the role of MRGPRX2 in type 2 inflammation development and cytokine release in AD by determining its levels in patients with AD and healthy controls. Furthermore, MrgprB2-conditional knockout (MrgprB2-/-) and wild-type mice were used to construct an MC903-induced AD mouse model to observe skin inflammation and cytokine release. Tryptase and its antagonist were applied separately to MrgprB2-/- mice with AD and wild-type mice with AD to confirm the role of the MRGPRB2-tryptase axis in the development of type 2 inflammation in AD. We found that AD severity and type 2 cytokine levels were not associated with IgE levels but were associated with MRGPRX2/MRGPRB2 expression. MrgprB2-/- mice with AD showed milder phenotypes and inflammatory infiltration in the skin than wild-type mice with AD. Tryptase released by MRGPRX2/MRGPRB2 activation is involved in the release of type 2 cytokines, which contributes to inflammatory development in AD. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Tao Jia, Delu Che, Yi Zheng, Huan Zhang, Yaxiang Li, Tong Zhou, Bin Peng, Xueshan Du, Longfei Zhu, Jingang An, Songmei Geng. Mast Cells Initiate Type 2 Inflammation through Tryptase Released by MRGPRX2/MRGPRB2 Activation in Atopic Dermatitis. The Journal of investigative dermatology. 2024 Jan;144(1):53-62.e2

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PMID: 37482287

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