TY - JOUR
T1 - C-reactive protein controls il-23 production by human monocytes
AU - Geyer, Chiara E.
AU - Newling, Melissa
AU - Sritharan, Lathees
AU - Griffith, Guillermo R.
AU - Chen, Hung-Jen
AU - Baeten, Dominique L. P.
AU - den Dunnen, Jeroen
N1 - Funding Information: Funding: This research was funded by the Dutch Arthritis Foundation (ReumaNederland, grant number 14-2-302), European Union’s Horizon 2020 research and innovation programme (“ARCAID”; www.arcaid-h2020.eu, accessed on 1 September 2021; grant number 847551) and the Academic Medical Center (AMC Fellowship 2015). D.L.P.B. is also an employee of Union Chimique Belge. The other authors have no potential financial conflicts of interest. Funding Information: This research was funded by the Dutch Arthritis Foundation (ReumaNederland, grant number 14-2-302), European Union?s Horizon 2020 research and innovation programme (?ARCAID?; www.arcaid-h2020.eu, accessed on 1 September 2021; grant number 847551) and the Academic Medical Center (AMC Fellowship 2015). D.L.P.B. is also an employee of Union Chimique Belge. The other authors have no potential financial conflicts of interest. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - C-reactive protein (CRP) is an acute-phase protein in humans that is produced in high quantities by the liver upon infection and under inflammatory conditions. Although CRP is commonly used as a marker of inflammation, CRP can also directly contribute to inflammation by eliciting pro-inflammatory cytokine production by immune cells. Since CRP is highly elevated in serum under inflammatory conditions, we have studied the CRP-induced cytokine profile of human monocytes, one of the main innate immune cell populations in blood. We identified that CRP is relatively unique in its capacity to induce production of the pro-inflammatory cytokine IL-23, which was in stark contrast to a wide panel of pattern recognition receptor (PRR) ligands. We show that CRP-induced IL-23 production was mediated at the level of gene transcription, since CRP particularly promoted gene transcription of IL23A (encoding IL-23p19) instead of IL12A (encoding IL-12p35), while PRR ligands induce the opposite response. Interestingly, when CRP stimulation was combined with PRR ligand stimulation, as for example, occurs in the context of sepsis, IL-23 production by monocytes was strongly reduced. Combined, these data identify CRP as a unique individual ligand to induce IL-23 production by monocytes, which may contribute to shaping systemic immune responses under inflammatory conditions.
AB - C-reactive protein (CRP) is an acute-phase protein in humans that is produced in high quantities by the liver upon infection and under inflammatory conditions. Although CRP is commonly used as a marker of inflammation, CRP can also directly contribute to inflammation by eliciting pro-inflammatory cytokine production by immune cells. Since CRP is highly elevated in serum under inflammatory conditions, we have studied the CRP-induced cytokine profile of human monocytes, one of the main innate immune cell populations in blood. We identified that CRP is relatively unique in its capacity to induce production of the pro-inflammatory cytokine IL-23, which was in stark contrast to a wide panel of pattern recognition receptor (PRR) ligands. We show that CRP-induced IL-23 production was mediated at the level of gene transcription, since CRP particularly promoted gene transcription of IL23A (encoding IL-23p19) instead of IL12A (encoding IL-12p35), while PRR ligands induce the opposite response. Interestingly, when CRP stimulation was combined with PRR ligand stimulation, as for example, occurs in the context of sepsis, IL-23 production by monocytes was strongly reduced. Combined, these data identify CRP as a unique individual ligand to induce IL-23 production by monocytes, which may contribute to shaping systemic immune responses under inflammatory conditions.
KW - C-reactive protein
KW - Fc receptor
KW - IL-23
KW - Inflammation
KW - Inflammatory bowel disease
KW - Monocyte
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=85117879812&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms222111638
DO - https://doi.org/10.3390/ijms222111638
M3 - Article
C2 - 34769069
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 21
M1 - 11638
ER -