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Updated: May 11, 2026

Isolation of Leukocytes from the Murine Tissues at the Maternal-Fetal Interface
Published on: May 21, 2015
Interleukin-10 regulates the fetal hyaluronan-rich extracellular matrix via a STAT3-dependent mechanism
Alice King1, Swathi Balaji, Emily Marsh
1The Center for Molecular Fetal Therapy, Division of Pediatric, Thoracic and General Surgery, Cincinnati Children's Hospital and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039, USA.
Background:
The midgestational fetus is capable of regenerative healing. We have recently demonstrated a novel role for the anti-inflammatory cytokine interleukin 10 (IL-10) as a regulator of hyaluronan (HA) in the extracellular matrix. The signaling pathway of IL-10 has been studied in monocytes but is unknown in dermal fibroblasts. We hypothesized IL-10 signals through its primary receptor, IL-10R1, to activate STAT3, resulting in HA synthesis.
Methods:
Murine midgestational (E14.5) fetal fibroblasts were evaluated in vitro. Pericellular matrix was quantified using a particle exclusion assay. STAT3 levels and cellular localization were evaluated by Western blot/band densitometry and immunocytochemistry/confocal microscopy. HA levels were quantified by enzyme-linked immunosorbent assay. The effects of IL-10R1 signal blockade by a neutralizing antibody and STAT3 inhibition were evaluated. An ex vivo midgestation fetal forearm culture incisional wound model in control and transgenic IL-10-/- mice was used to evaluate the role of STAT3 on the extracellular matrix.
Results:
Fetal fibroblasts produce a robust hyaluronan-rich pericellular matrix that is IL-10R1 and STAT3 dependent. Inhibition of IL-10R1 signaling results in decreased phosphorylated STAT3 levels and inhibition of nuclear localization. Inhibition of STAT3 results in decreased HA production. At day 3, midgestation fetal wounds have efficient re-epithelialization, which is significantly slowed in IL-10-/- wounds at the same gestation and with inhibition of STAT3.
Conclusions:
Our data demonstrate that IL-10 regulates HA synthesis through its primary receptor IL-10R1 and STAT3 activation. This supports a novel nonimmunoregulatory mechanism of IL-10 in its role in fetal regenerative wound healing.
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