PMID- 30967512 OWN - NLM STAT- MEDLINE DCOM- 20200629 LR - 20200629 IS - 1937-9145 (Electronic) IS - 1945-0877 (Linking) VI - 12 IP - 576 DP - 2019 Apr 9 TI - Pivotal role of STIM2, but not STIM1, in IL-4 production by IL-3-stimulated murine basophils. LID - eaav2060 [pii] LID - 10.1126/scisignal.aav2060 [doi] AB - Basophils have nonredundant roles in various immune responses that require Ca(2+) influx. Here, we examined the role of two Ca(2+) sensors, stromal interaction molecule 1 and 2 (STIM1 and STIM2), in basophil activation. We found that loss of STIM1, but not STIM2, impaired basophil IL-4 production after stimulation with immunoglobulin E (IgE)-containing immune complexes. In contrast, when basophils were stimulated with IL-3, loss of STIM2, but not STIM1, reduced basophil IL-4 production. This difference in STIM proteins was associated with distinct time courses of Ca(2+) influx and transcription of the Il4 gene that were elicited by each stimulus. Similarly, basophil-specific STIM1 expression was required for IgE-driven chronic allergic inflammation in vivo, whereas STIM2 was required for IL-4 production after combined IL-3 and IL-33 treatment in mice. These data indicate that STIM1 and STIM2 have differential roles in the production of IL-4, which are stimulus dependent. Furthermore, these results illustrate the vital role of STIM2 in basophils, which is often considered to be less important than STIM1. CI - Copyright (c) 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. FAU - Yoshikawa, Soichiro AU - Yoshikawa S AUID- ORCID: 0000-0003-1820-3829 AD - Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. yoshisou.mbch@tmd.ac.jp. FAU - Oh-Hora, Masatsugu AU - Oh-Hora M AD - Department of Biochemistry, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan. FAU - Hashimoto, Ryota AU - Hashimoto R AUID- ORCID: 0000-0003-0983-6704 AD - Department of Physiology, Faculty of Medicine, Juntendo University, Tokyo 113-8421, Japan. FAU - Nagao, Toshihisa AU - Nagao T AUID- ORCID: 0000-0003-2597-0719 AD - Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. FAU - Peters, Louis AU - Peters L AD - Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. AD - Faculty of Medicine, Imperial College London, London SW7 2BX, UK. FAU - Egawa, Mayumi AU - Egawa M AUID- ORCID: 0000-0001-5806-0039 AD - Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. FAU - Ohta, Takuya AU - Ohta T AUID- ORCID: 0000-0002-4174-6349 AD - Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. FAU - Miyake, Kensuke AU - Miyake K AUID- ORCID: 0000-0003-1149-3755 AD - Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. FAU - Adachi, Takahiro AU - Adachi T AUID- ORCID: 0000-0002-3711-8577 AD - Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. FAU - Kawano, Yohei AU - Kawano Y AD - Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. FAU - Yamanishi, Yoshinori AU - Yamanishi Y AUID- ORCID: 0000-0002-9598-3542 AD - Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. FAU - Karasuyama, Hajime AU - Karasuyama H AUID- ORCID: 0000-0003-0689-0836 AD - Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190409 PL - United States TA - Sci Signal JT - Science signaling JID - 101465400 RN - 0 (Il4 protein, mouse) RN - 0 (Interleukin-3) RN - 0 (Stim1 protein, mouse) RN - 0 (Stim2 protein, mouse) RN - 0 (Stromal Interaction Molecule 1) RN - 0 (Stromal Interaction Molecule 2) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Animals MH - Basophils/cytology/*immunology MH - Calcium Signaling/genetics/*immunology MH - Immunoglobulin E/immunology MH - Interleukin-3/genetics/*immunology MH - Interleukin-4/genetics/*immunology MH - Mice MH - Mice, Knockout MH - Stromal Interaction Molecule 1/genetics/*immunology MH - Stromal Interaction Molecule 2/genetics/*immunology EDAT- 2019/04/11 06:00 MHDA- 2020/07/01 06:00 CRDT- 2019/04/11 06:00 PHST- 2019/04/11 06:00 [entrez] PHST- 2019/04/11 06:00 [pubmed] PHST- 2020/07/01 06:00 [medline] AID - 12/576/eaav2060 [pii] AID - 10.1126/scisignal.aav2060 [doi] PST - epublish SO - Sci Signal. 2019 Apr 9;12(576):eaav2060. doi: 10.1126/scisignal.aav2060.