Details

Autor(en) / Beteiligte

• Irie, Misato
• Kabata, Hiroki
• Sasahara, Kotaro
• Kurihara, Momoko
• Shirasaki, Yoshitaka
• Kamatani, Takashi
• Baba, Rie
• Matsusaka, Masako
• Koga, Satoshi
• Masaki, Katsunori
• Miyata, Jun
• Araki, Yasutomo
• Kikawada, Toru
• Kabe, Yasuaki
• Suematsu, Makoto
• Yamagishi, Mai
• Uemura, Sotaro
• Moro, Kazuyo
• Fukunaga, Koichi

Titel

Annexin A1 is a cell-intrinsic metalloregulator of zinc in human ILC2s

Ist Teil von

• Cell reports (Cambridge), 2023-06, Vol.42 (6), p.112610-112610, Article 112610

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Group 2 innate lymphoid cells (ILC2s) produce large amounts of type 2 cytokines including interleukin-5 (IL-5) and IL-13 in response to various stimuli, causing allergic and eosinophilic diseases. However, the cell-intrinsic regulatory mechanisms of human ILC2s remain unclear. Here, we analyze human ILC2s derived from different tissues and pathological conditions and identify ANXA1, encoding annexin A1, as a commonly highly expressed gene in non-activated ILC2s. The expression of ANXA1 decreases when ILC2s activate, but it increases autonomously as the activation subsides. Lentiviral vector-based gene transfer experiments show that ANXA1 suppresses the activation of human ILC2s. Mechanistically, ANXA1 regulates the expression of the metallothionein family genes, including MT2A, which modulate intracellular zinc homeostasis. Furthermore, increased intracellular zinc levels play an essential role in the activation of human ILC2s by promoting the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and GATA3 expression. Thus, the ANXA1/MT2A/zinc pathway is identified as a cell-intrinsic metalloregulatory mechanism for human ILC2s. [Display omitted] •ANXA1, which encodes annexin A1, is highly expressed in non-activated ILC2s•ANXA1 suppresses the activation of human and mouse ILC2s•ANXA1 regulates metallothionein to modulate intracellular zinc levels•Zinc is essential for the activation of human ILC2s via multiple signaling pathways Group 2 innate lymphoid cells (ILC2s) are involved in various allergic diseases. Irie et al. show that annexin A1 (ANXA1) is a biomarker for non-activated ILC2s and that it regulates the expression of metallothionein to modulate the intracellular zinc levels of ILC2s, thereby controlling their activation.