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Enhanced STAT3 phosphorylation and PD-L1 expression in myeloid dendritic cells indicate impaired IL-27Ralpha signaling in type 1 diabetes.


ABSTRACT: Interleukin 27 (IL-27), a member of the IL-12 family, is important for T cell differentiation; however, little is known about its effect on dendritic cells (DCs). IL-27 can activate multiple signaling cascades, including the JAK/STAT pathway, and depending on the setting it can both promote and antagonize inflammatory responses. An anti-inflammatory function of IL-27 has been reported in several autoimmune diseases; however, in type 1 diabetes (T1D), an autoimmune disease where autoreactive cytotoxic T cells attack insulin-producing beta cells, IL-27 has been shown to have a dual role and contradictory effects. Here, we show impaired IL-27 signaling in a large cohort of T1D patients (n?=?51) compared to age- and gender-matched healthy donors. Increased expression of the IL-27 receptor subunit IL-27Ralpha mRNA in purified myeloid DCs (mDCs), detected by gene expression microarrays was mirrored by enhanced signal transduction in T1D mDCs in response to IL-27 stimulation. Higher STAT phosphorylation in T1D patients was also accompanied by elevated expression of the inhibitory molecules PD-L1, PD-L2 and PD-1, which may suggest not only immunomodulatory mechanisms of IL-27 in T1D but also a compensatory effort of T1D dendritic cells against the ongoing inflammation.

SUBMITTER: Parackova Z 

PROVIDER: S-EPMC6965661 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Enhanced STAT3 phosphorylation and PD-L1 expression in myeloid dendritic cells indicate impaired IL-27Ralpha signaling in type 1 diabetes.

Parackova Z Z   Vrabcova P P   Zentsova I I   Kayserova J J   Richtrova I I   Sojka L L   Stechova K K   Sumnik Z Z   Sediva A A  

Scientific reports 20200116 1


Interleukin 27 (IL-27), a member of the IL-12 family, is important for T cell differentiation; however, little is known about its effect on dendritic cells (DCs). IL-27 can activate multiple signaling cascades, including the JAK/STAT pathway, and depending on the setting it can both promote and antagonize inflammatory responses. An anti-inflammatory function of IL-27 has been reported in several autoimmune diseases; however, in type 1 diabetes (T1D), an autoimmune disease where autoreactive cyto  ...[more]

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