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Separation of the Ca V 1.2-Ca V 1.3 calcium channel duo prevents type 2 allergic airway inflammation.
- Source :
-
Allergy [Allergy] 2022 Feb; Vol. 77 (2), pp. 525-539. Date of Electronic Publication: 2021 Jul 09. - Publication Year :
- 2022
-
Abstract
- Background: Voltage-gated calcium (Ca <subscript>v</subscript> 1) channels contribute to T-lymphocyte activation. Ca <subscript>v</subscript> 1.2 and Ca <subscript>v</subscript> 1.3 channels are expressed in Th2 cells but their respective roles are unknown, which is investigated herein.<br />Methods: We generated mice deleted for Ca <subscript>v</subscript> 1.2 in T cells or Ca <subscript>v</subscript> 1.3 and analyzed TCR-driven signaling. In this line, we developed original fast calcium imaging to measure early elementary calcium events (ECE). We also tested the impact of Ca <subscript>v</subscript> 1.2 or Ca <subscript>v</subscript> 1.3 deletion in models of type 2 airway inflammation. Finally, we checked whether the expression of both Ca <subscript>v</subscript> 1.2 and Ca <subscript>v</subscript> 1.3 in T cells from asthmatic children correlates with Th2-cytokine expression.<br />Results: We demonstrated non-redundant and synergistic functions of Ca <subscript>v</subscript> 1.2 and Ca <subscript>v</subscript> 1.3 in Th2 cells. Indeed, the deficiency of only one channel in Th2 cells triggers TCR-driven hyporesponsiveness with weakened tyrosine phosphorylation profile, a strong decrease in initial ECE and subsequent reduction in the global calcium response. Moreover, Ca <subscript>v</subscript> 1.3 has a particular role in calcium homeostasis. In accordance with the singular roles of Ca <subscript>v</subscript> 1.2 and Ca <subscript>v</subscript> 1.3 in Th2 cells, deficiency in either one of these channels was sufficient to inhibit cardinal features of type 2 airway inflammation. Furthermore, Ca <subscript>v</subscript> 1.2 and Ca <subscript>v</subscript> 1.3 must be co-expressed within the same CD4 <superscript>+</superscript> T cell to trigger allergic airway inflammation. Accordingly with the concerted roles of Ca <subscript>v</subscript> 1.2 and Ca <subscript>v</subscript> 1.3, the expression of both channels by activated CD4 <superscript>+</superscript> T cells from asthmatic children was associated with increased Th2-cytokine transcription.<br />Conclusions: Thus, Ca <subscript>v</subscript> 1.2 and Ca <subscript>v</subscript> 1.3 act as a duo, and targeting only one of these channels would be efficient in allergy treatment.<br /> (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Details
- Language :
- English
- ISSN :
- 1398-9995
- Volume :
- 77
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Allergy
- Publication Type :
- Academic Journal
- Accession number :
- 34181765
- Full Text :
- https://doi.org/10.1111/all.14993