Publications by authors named "Marine Babin"

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Ca1.4 calcium channels control cytokine production by human peripheral T17 cells and psoriatic skin-infiltrating T cells.

J Allergy Clin Immunol 2021 Oct 13. Epub 2021 Oct 13.

Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, Centre National de la Recherche Scientifique UMR5051, University Paul Sabatier Toulouse III, Toulouse, France. Electronic address:

Background: Type-17 inflammation characterizes psoriasis, a chronic skin disease. Because several inflammatory cytokines contribute to psoriasis pathogenesis, inhibiting the simultaneous production of these cytokines in T17 cells may be beneficial in psoriasis. We found that Ca1.4, encoded by CACNA1F, was the only Ca1 calcium channel expressed in T17 cells.

Objective: We sought to investigate the role of Ca1.4 expression in early T17-activation events and effector functions, as well as its association with T17 signature genes in lesional psoriatic (LP) skins.

Methods: Transcriptional gene signatures associated with CACNA1F expression were examined in LP skins by RT-PCR and in situ hybridization. Ca1 inhibitor and/or shRNA lentivectors were used to assess the contribution of Ca1.4 in T17 activation and effector functions in a 3-dimensional skin reconstruction model.

Results: CACNA1F expression correlated with inflammatory cytokine expression that characterizes LP skins and was preferentially associated with RORC expression in CD4 and CD4 cells from LP biopsies. Nicardipine, a Ca1 channel antagonist, markedly reduced inflammatory cytokine production by T17 cells from blood or LP skin. This was associated with decreased TCR-induced early calcium events at cell membrane and proximal signaling events. The knockdown of Ca1.4 in T17 cells impaired cytokine production. Finally, Ca1 inhibition reduced the expression of the keratinocyte genes characteristic of T17-mediated psoriasis inflammation in human skin equivalents.

Conclusions: Ca1.4 channels promote T17-cell functions both at the periphery and in inflammatory psoriatic skin.
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http://dx.doi.org/10.1016/j.jaci.2021.09.030DOI Listing
October 2021
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