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  • Cutting Edge: MMP-9 inhibits IL-23p19 expression in dendritic cells by targeting membrane stem cell factor affecting lung IL-17 response.

Cutting Edge: MMP-9 inhibits IL-23p19 expression in dendritic cells by targeting membrane stem cell factor affecting lung IL-17 response.

Journal of immunology (Baltimore, Md. : 1950) (2014-05-16)
Timothy B Oriss, Nandini Krishnamoorthy, Mahesh Raundhal, Christina Morse, Krishnendu Chakraborty, Anupriya Khare, Rachael Huff, Prabir Ray, Anuradha Ray
ABSTRACT

We reported previously that c-kit ligation by membrane-bound stem cell factor (mSCF) boosts IL-6 production in dendritic cells (DCs) and a Th17-immune response. However, Th17 establishment also requires heterodimeric IL-23, but the mechanisms that regulate IL-23 gene expression in DCs are not fully understood. We show that IL-23p19 gene expression in lung DCs is dependent on mSCF, which is regulated by the metalloproteinase MMP-9. Th1-inducing conditions enhanced MMP-9 activity, causing cleavage of mSCF, whereas the opposite was true for Th17-promoting conditions. In MMP-9(-/-) mice, a Th1-inducing condition could maintain mSCF and enhance IL-23p19 in DCs, promoting IL-17-producing CD4(+) T cells in the lung. Conversely, mSCF cleavage from bone marrow DCs in vitro by rMMP-9 led to reduced IL-23p19 expression under Th17-inducing conditions, with dampening of intracellular AKT phosphorylation. Collectively, these results show that the c-kit/mSCF/MMP-9 axis regulates IL-23 gene expression in DCs to control IL-17 production in the lung.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Mouse SCF ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Human SCF ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Human IL-17 ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
β-D-Allose, rare aldohexose sugar
Sigma-Aldrich
Mouse IL-17 (IL-17A) ELISA Kit, for serum, plasma and cell culture supernatant