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Related Experiment Video

Updated: Oct 13, 2025

A Strategy for the Study of IL-9-Producing Lymphoid Cells in the Nippostrongylus brasiliensis Infection Model
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IL-13 Controls IL-33 Activity through Modulation of ST2.

Melvin Zhang1, Jennifer L Duffen1, Karl H Nocka1

  • 1Inflammation and Immunology Research Unit, Pfizer, Inc., Cambridge, MA.

Journal of Immunology (Baltimore, Md. : 1950)
|November 18, 2021
PubMed
Summary
This summary is machine-generated.

Interleukin-13 (IL-13) regulates Interleukin-33 (IL-33) activity by increasing the decoy receptor soluble ST2 (sST2) and modulating ST2L+ group 2 innate lymphoid cells (ILC2s). This impacts inflammation and immune cell responses.

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Area of Science:

  • Immunology
  • Inflammation research
  • Cytokine signaling

Background:

  • Interleukin-33 (IL-33) is a key cytokine in local inflammation, acting on cells like ILC2s, Th2 cells, and mast cells.
  • IL-33 signaling is modulated by transmembrane ST2L and its decoy receptor, soluble ST2 (sST2).
  • Previous studies suggested a role for IL-13 in modulating IL-33 responsiveness, but the precise mechanisms were unclear.

Purpose of the Study:

  • To investigate the regulatory role of IL-13 on IL-33 activity.
  • To determine if IL-13 modulates the expression of transmembrane ST2L and soluble ST2 (sST2).
  • To elucidate the cellular mechanisms by which IL-13 influences IL-33-mediated responses.

Main Methods:

  • Utilized Il13 knockout (Il13-/-) mice and wild-type (WT) littermates.
  • Administered IL-33 intraperitoneally (i.p.) to assess inflammatory and immune responses.
  • Analyzed splenomegaly, immune cell populations in the peritoneum and spleen, eosinophilia, sST2 levels, and gene expression of ST2 isoforms in various tissues.

Main Results:

  • Il13-/- mice exhibited exacerbated responses to IL-33 compared to WT mice.
  • IL-33 administration led to heightened splenomegaly, increased peritoneal immune cells including ST2L+ ILC2s, and elevated eosinophilia in Il13-/- mice.
  • Reduced levels of sST2 were observed in the circulation and peritoneum of Il13-/- mice, with increased gene expression of both ST2 isoforms in spleen, lung, and liver.
  • Fibroblasts were identified as IL-13-responsive cells that regulate IL-33 activity via sST2 production.

Conclusions:

  • IL-13 plays a significant regulatory role in IL-33-mediated inflammation.
  • IL-13 induces the production of the IL-33 decoy receptor sST2, thereby dampening IL-33 signaling.
  • IL-13 also modulates ST2L+ ILC2 populations, further influencing the immune response to IL-33.