TMPRSS2 Impacts Cytokine Expression in Murine Dendritic Cells

Area of Science:

• Immunology
• Virology
• Protease Function

Background:

• Transmembrane protease serine 2 (TMPRSS2) is crucial for viral entry.
• Targeting host proteins like TMPRSS2 for antivirals may cause immune side effects.
• The role of TMPRSS2 in dendritic cell (DC) function requires further investigation.

Purpose of the Study:

• To investigate the impact of TMPRSS2 genetic deletion on dendritic cell (DC) function.
• To analyze cytokine production and gene expression in DCs lacking TMPRSS2.
• To understand the differential effects of TMPRSS2 on plasmacytoid DCs (pDCs) and classical DCs (cDCs).

Main Methods:

• Differentiated bone marrow cells from wild-type (WT) and TMPRSS2-deficient (TMPRSS2-/-) mice into pDCs and cDCs.
• Activated DCs using various toll-like receptor (TLR) agonists (resiquimod, ODN 1668).
• Analyzed cytokine release and mRNA expression of key immune-related genes.

Main Results:

• In cDCs, TMPRSS2 deficiency increased IL-12 and IFNγ upon TLR7/8 or TLR9 activation, with reduced IL-10.
• In pDCs, TMPRSS2 deficiency decreased IL-6, IL-10, and IFNγ with resiquimod activation.
• TMPRSS2 deficiency led to reduced IFNα in pDCs activated by ODN 1668, with minimal effects on receptor expression.

Conclusions:

• TMPRSS2 influences DC cytokine release in a TLR-dependent manner.
• TMPRSS2 exhibits distinct roles in pDCs and cDCs, potentially suppressing cytokine release in cDCs and mediating it in pDCs.