Protein kinase C theta is required for efficient induction of IL-10-secreting T cells.
Secretion of interleukin-10 (IL-10) by CD4+ T cells is an essential immunoregulatory mechanism. The work presented here assesses the role of the signaling molecule protein kinase C theta (PKCθ) in the induction of IL-10 expression in CD4+ T cells. Using wildtype and PKCθ-deficient Tg4 T cell recepto...
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
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| author | Graham J Britton Ruth E Mitchell Bronwen R Burton David C Wraith |
| author_facet | Graham J Britton Ruth E Mitchell Bronwen R Burton David C Wraith |
| author_sort | Graham J Britton |
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| description | Secretion of interleukin-10 (IL-10) by CD4+ T cells is an essential immunoregulatory mechanism. The work presented here assesses the role of the signaling molecule protein kinase C theta (PKCθ) in the induction of IL-10 expression in CD4+ T cells. Using wildtype and PKCθ-deficient Tg4 T cell receptor transgenic mice, we implemented a well-described protocol of repeated doses of myelin basic protein (MBP)Ac1-9[4Y] antigen to induce Tr1-like IL-10+ T cells. We find that PKCθ is required for the efficient induction of IL-10 following antigen administration. Both serum concentrations of IL-10 and the proportion of IL-10+ T cells were reduced in PKCθ-deficient mice relative to wildtype mice following [4Y] treatment. We further characterized the T cells of [4Y] treated PKCθ-deficient Tg4 mice and found reduced expression of the transcription factors cMaf, Nfil3 and FoxP3 and the surface receptors PD-1 and Tim3, all of which have been associated with the differentiation or function of IL-10+ T cells. Finally, we demonstrated that, unlike [4Y] treated wildtype Tg4 T cells, cells from PKCθ-deficient mice were unable to suppress the priming of naïve T cells in vitro and in vivo. In summary, we present data demonstrating a role for PKCθ in the induction of suppressive, IL-10-secreting T cells induced in TCR-transgenic mice following chronic antigen administration. This should be considered when contemplating PKCθ as a suitable drug target for inducing immune suppression and graft tolerance. |
| format | Article |
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| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-fd3edca46cd7492d8a7fdd0143f3513d2025-08-20T02:31:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017154710.1371/journal.pone.0171547Protein kinase C theta is required for efficient induction of IL-10-secreting T cells.Graham J BrittonRuth E MitchellBronwen R BurtonDavid C WraithSecretion of interleukin-10 (IL-10) by CD4+ T cells is an essential immunoregulatory mechanism. The work presented here assesses the role of the signaling molecule protein kinase C theta (PKCθ) in the induction of IL-10 expression in CD4+ T cells. Using wildtype and PKCθ-deficient Tg4 T cell receptor transgenic mice, we implemented a well-described protocol of repeated doses of myelin basic protein (MBP)Ac1-9[4Y] antigen to induce Tr1-like IL-10+ T cells. We find that PKCθ is required for the efficient induction of IL-10 following antigen administration. Both serum concentrations of IL-10 and the proportion of IL-10+ T cells were reduced in PKCθ-deficient mice relative to wildtype mice following [4Y] treatment. We further characterized the T cells of [4Y] treated PKCθ-deficient Tg4 mice and found reduced expression of the transcription factors cMaf, Nfil3 and FoxP3 and the surface receptors PD-1 and Tim3, all of which have been associated with the differentiation or function of IL-10+ T cells. Finally, we demonstrated that, unlike [4Y] treated wildtype Tg4 T cells, cells from PKCθ-deficient mice were unable to suppress the priming of naïve T cells in vitro and in vivo. In summary, we present data demonstrating a role for PKCθ in the induction of suppressive, IL-10-secreting T cells induced in TCR-transgenic mice following chronic antigen administration. This should be considered when contemplating PKCθ as a suitable drug target for inducing immune suppression and graft tolerance.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171547&type=printable |
| spellingShingle | Graham J Britton Ruth E Mitchell Bronwen R Burton David C Wraith Protein kinase C theta is required for efficient induction of IL-10-secreting T cells. PLoS ONE |
| title | Protein kinase C theta is required for efficient induction of IL-10-secreting T cells. |
| title_full | Protein kinase C theta is required for efficient induction of IL-10-secreting T cells. |
| title_fullStr | Protein kinase C theta is required for efficient induction of IL-10-secreting T cells. |
| title_full_unstemmed | Protein kinase C theta is required for efficient induction of IL-10-secreting T cells. |
| title_short | Protein kinase C theta is required for efficient induction of IL-10-secreting T cells. |
| title_sort | protein kinase c theta is required for efficient induction of il 10 secreting t cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171547&type=printable |
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