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- Title
Elevated receptor for activated C kinase 1 expression is involved in intracellular Ca<sup>2+</sup> influx and potentially associated with compromised regulatory T cell function in patients with asthma.
- Authors
Negoro, T.; Shimizu, S.; Narushima, M.; Banham, A. H.; Wakabayashi, H.; Takayanagi, R.; Hagiwara, T.; Roncador, G.; Osabe, T.; Yanai, T.; Kin, M.; Ikeda, K.; Endo, A.; Akiyama, H.; Nakano, Y.
- Abstract
Background Regulatory T cells (Tregs) are activated during anergy in response to T cell receptor ( TCR) activation and functional immune suppression. Anergy of paediatric Tregs is partially dependent on intracellular calcium mobility; following TCR activation, Tregs do not exhibit increased intracellular Ca2+ concentration ([Ca2+]i). Objective We determined whether [Ca2+]i in adult Tregs defined their anergy, if intracellular Ca2+ movement was linked to regulatory functions, whether [Ca2+]i was indicative of asthma pathology, and the potential molecular mechanism responsible for Ca2+ movement in Tregs. Methods Tregs were purified by the magnetic bead method, and their regulatory functions were assessed by monitoring carboxyfluorescein succinimidyl ester-labelled responder T cell proliferation. The Ca2+ response of Fura-2-labelled cells was measured using a video image analysis system. To analyse the functions of Tregs at the molecular level, we generated Jurkat Tet-On® clones with doxycycline (Dox)-induced forkhead box P3 ( FOXP3) protein expression. Results CD4+ CD25+ CD127−/low Tregs from participants without asthma did not elicit Ca2+ influx in response to TCR activation, exhibited little proliferation and suppressed proliferation of CD4+ CD25− T cells. In contrast, under similar conditions, Tregs from patients with asthma exhibited increased [Ca2+]i and robust proliferation with partial loss of regulatory functions. FOXP3 protein levels in Tet-On® clones were high after both 2- and 5-day Dox treatment; however, 5-day cells were comparable with Tregs from patients with asthma, whereas 2-day cells were similar to Tregs from participants without asthma. Increasing [Ca2+]i induced a high level of receptor for activated C kinase 1 ( RACK1) expression in 5-day cells. Conclusions and Clinical Relevance We confirmed that Tregs in patients with asthma are functionally impaired and that the abnormal regulatory functions of these cells can be analysed by [Ca2+]i following TCR engagement. Furthermore, the impaired functioning of Tregs evident in patients with asthma may be due to a high level of RACK1.
- Subjects
T cells; KINASES; ASTHMA; INPATIENT care; ADENOSINE kinase
- Publication
Clinical & Experimental Allergy, 2014, Vol 44, Issue 9, p1154
- ISSN
0954-7894
- Publication type
Article
- DOI
10.1111/cea.12375