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Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10

Research output: Contribution to journalArticle

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Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10. / Dimeloe, Sarah; Rice, Louise V.; Chen, Hebe; Cheadle, Charlotte; Raynes, John; Pfeffer, Paul; Lavender, Paul; Richards, David F.; Nyon, Mun Peak; Mcdonnell, James M.; Kemper, Claudia; Gooptu, Bibek; Hawrylowicz, Catherine M.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 189, SBMB_2018_497, 05.2019, p. 1-9.

Research output: Contribution to journalArticle

Harvard

Dimeloe, S, Rice, LV, Chen, H, Cheadle, C, Raynes, J, Pfeffer, P, Lavender, P, Richards, DF, Nyon, MP, Mcdonnell, JM, Kemper, C, Gooptu, B & Hawrylowicz, CM 2019, 'Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10', Journal of Steroid Biochemistry and Molecular Biology, vol. 189, SBMB_2018_497, pp. 1-9. https://doi.org/10.1016/j.jsbmb.2019.01.014

APA

Dimeloe, S., Rice, L. V., Chen, H., Cheadle, C., Raynes, J., Pfeffer, P., Lavender, P., Richards, D. F., Nyon, M. P., Mcdonnell, J. M., Kemper, C., Gooptu, B., & Hawrylowicz, C. M. (2019). Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10. Journal of Steroid Biochemistry and Molecular Biology, 189, 1-9. [SBMB_2018_497]. https://doi.org/10.1016/j.jsbmb.2019.01.014

Vancouver

Dimeloe S, Rice LV, Chen H, Cheadle C, Raynes J, Pfeffer P et al. Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10. Journal of Steroid Biochemistry and Molecular Biology. 2019 May;189:1-9. SBMB_2018_497. https://doi.org/10.1016/j.jsbmb.2019.01.014

Author

Dimeloe, Sarah ; Rice, Louise V. ; Chen, Hebe ; Cheadle, Charlotte ; Raynes, John ; Pfeffer, Paul ; Lavender, Paul ; Richards, David F. ; Nyon, Mun Peak ; Mcdonnell, James M. ; Kemper, Claudia ; Gooptu, Bibek ; Hawrylowicz, Catherine M. / Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10. In: Journal of Steroid Biochemistry and Molecular Biology. 2019 ; Vol. 189. pp. 1-9.

Bibtex Download

@article{f73c1d8d1cc04f64b674a252fb02b6ea,
title = "Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10",
abstract = "Studies to identify novel immune-regulatory functions of active vitamin D (1,25(OH)2D3) in human CD4+ T cells revealed that 1,25(OH)2D3 potently induced expression of the gene SERPINA1, encoding the anti-protease α-1-antitrypsin. We confirmed α-1-antitrypsin protein expression by 1,25(OH)2D3-treated CD4+ T cells, but not in CD8+ T cells or monocytes. α-1-antitrypsin promotes anti-inflammatory IL-10 synthesis in other immune cell populations. We therefore investigated its immune-regulatory effects in CD4+ T cells. Plasma-derived α-1-antitrypsin drove IL-10synthesis by CD4+ T cells, which was not dependent on anti-protease activity, but appeared to require a serum binding factor, since this could not be achieved with recombinant protein. α-1-antitrypsin is reported to bindcomplement components, which regulate T cell function. A role for this interaction was therefore probed. Plasmaderived, but not recombinant α-1-antitrypsin contained C3a. Surface Plasmon Resonance and MicroscaleThermophoresis demonstrated α-1-antitrypsin binding to C3a. Addition of C3a to CD4+ T cells cultured with recombinant α-1-antitrypsin restored induction of IL-10, whereas neutralisation of C3a abrogated IL-10 induced by plasma-derived α-1-antitrypsin. To interrogate an endogenous role for the α-1-antitrypsin-C3a axis in 1,25(OH)2D3-driven CD4+ T cell IL-10 synthesis, we treated cells from healthy or α-1-antitrypsin-deficient individuals (which transcribe SERPINA1 but do not secrete protein) with 1,25(OH)2D3. A significant correlation was identified betweenSERPINA1 and IL10 gene expression in healthy donor CD4+ T cells, which was absent in cells from α-1-antitrypsindeficient individuals. Therefore, α-1-antitrypsin is required for 1,25(OH)2D3-induced IL-10 expression in CD4+ T cells, interacting with C3a to drive IL-10 expression.",
keywords = "C3a, Complement, IL-10, Immune regulation, α-1-Antitrypsin",
author = "Sarah Dimeloe and Rice, {Louise V.} and Hebe Chen and Charlotte Cheadle and John Raynes and Paul Pfeffer and Paul Lavender and Richards, {David F.} and Nyon, {Mun Peak} and Mcdonnell, {James M.} and Claudia Kemper and Bibek Gooptu and Hawrylowicz, {Catherine M.}",
year = "2019",
month = may,
doi = "10.1016/j.jsbmb.2019.01.014",
language = "English",
volume = "189",
pages = "1--9",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10

AU - Dimeloe, Sarah

AU - Rice, Louise V.

AU - Chen, Hebe

AU - Cheadle, Charlotte

AU - Raynes, John

AU - Pfeffer, Paul

AU - Lavender, Paul

AU - Richards, David F.

AU - Nyon, Mun Peak

AU - Mcdonnell, James M.

AU - Kemper, Claudia

AU - Gooptu, Bibek

AU - Hawrylowicz, Catherine M.

PY - 2019/5

Y1 - 2019/5

N2 - Studies to identify novel immune-regulatory functions of active vitamin D (1,25(OH)2D3) in human CD4+ T cells revealed that 1,25(OH)2D3 potently induced expression of the gene SERPINA1, encoding the anti-protease α-1-antitrypsin. We confirmed α-1-antitrypsin protein expression by 1,25(OH)2D3-treated CD4+ T cells, but not in CD8+ T cells or monocytes. α-1-antitrypsin promotes anti-inflammatory IL-10 synthesis in other immune cell populations. We therefore investigated its immune-regulatory effects in CD4+ T cells. Plasma-derived α-1-antitrypsin drove IL-10synthesis by CD4+ T cells, which was not dependent on anti-protease activity, but appeared to require a serum binding factor, since this could not be achieved with recombinant protein. α-1-antitrypsin is reported to bindcomplement components, which regulate T cell function. A role for this interaction was therefore probed. Plasmaderived, but not recombinant α-1-antitrypsin contained C3a. Surface Plasmon Resonance and MicroscaleThermophoresis demonstrated α-1-antitrypsin binding to C3a. Addition of C3a to CD4+ T cells cultured with recombinant α-1-antitrypsin restored induction of IL-10, whereas neutralisation of C3a abrogated IL-10 induced by plasma-derived α-1-antitrypsin. To interrogate an endogenous role for the α-1-antitrypsin-C3a axis in 1,25(OH)2D3-driven CD4+ T cell IL-10 synthesis, we treated cells from healthy or α-1-antitrypsin-deficient individuals (which transcribe SERPINA1 but do not secrete protein) with 1,25(OH)2D3. A significant correlation was identified betweenSERPINA1 and IL10 gene expression in healthy donor CD4+ T cells, which was absent in cells from α-1-antitrypsindeficient individuals. Therefore, α-1-antitrypsin is required for 1,25(OH)2D3-induced IL-10 expression in CD4+ T cells, interacting with C3a to drive IL-10 expression.

AB - Studies to identify novel immune-regulatory functions of active vitamin D (1,25(OH)2D3) in human CD4+ T cells revealed that 1,25(OH)2D3 potently induced expression of the gene SERPINA1, encoding the anti-protease α-1-antitrypsin. We confirmed α-1-antitrypsin protein expression by 1,25(OH)2D3-treated CD4+ T cells, but not in CD8+ T cells or monocytes. α-1-antitrypsin promotes anti-inflammatory IL-10 synthesis in other immune cell populations. We therefore investigated its immune-regulatory effects in CD4+ T cells. Plasma-derived α-1-antitrypsin drove IL-10synthesis by CD4+ T cells, which was not dependent on anti-protease activity, but appeared to require a serum binding factor, since this could not be achieved with recombinant protein. α-1-antitrypsin is reported to bindcomplement components, which regulate T cell function. A role for this interaction was therefore probed. Plasmaderived, but not recombinant α-1-antitrypsin contained C3a. Surface Plasmon Resonance and MicroscaleThermophoresis demonstrated α-1-antitrypsin binding to C3a. Addition of C3a to CD4+ T cells cultured with recombinant α-1-antitrypsin restored induction of IL-10, whereas neutralisation of C3a abrogated IL-10 induced by plasma-derived α-1-antitrypsin. To interrogate an endogenous role for the α-1-antitrypsin-C3a axis in 1,25(OH)2D3-driven CD4+ T cell IL-10 synthesis, we treated cells from healthy or α-1-antitrypsin-deficient individuals (which transcribe SERPINA1 but do not secrete protein) with 1,25(OH)2D3. A significant correlation was identified betweenSERPINA1 and IL10 gene expression in healthy donor CD4+ T cells, which was absent in cells from α-1-antitrypsindeficient individuals. Therefore, α-1-antitrypsin is required for 1,25(OH)2D3-induced IL-10 expression in CD4+ T cells, interacting with C3a to drive IL-10 expression.

KW - C3a

KW - Complement

KW - IL-10

KW - Immune regulation

KW - α-1-Antitrypsin

UR - http://www.scopus.com/inward/record.url?scp=85061024390&partnerID=8YFLogxK

U2 - 10.1016/j.jsbmb.2019.01.014

DO - 10.1016/j.jsbmb.2019.01.014

M3 - Article

VL - 189

SP - 1

EP - 9

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

M1 - SBMB_2018_497

ER -

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