2. Academic Validation
  3. The RNA-binding protein KSRP reduces asthma-like characteristics in a murine model

The RNA-binding protein KSRP reduces asthma-like characteristics in a murine model

  • Inflamm Res. 2025 Mar 17;74(1):54. doi: 10.1007/s00011-025-02024-5.
Kim-Alicia Palzer 1,  Vanessa Bolduan 2,  Jelena Lakus 3,  Ingrid Tubbe 2,  Evelyn Montermann 2,  Björn E Clausen 3,  Matthias Bros 2,  Andrea Pautz 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, University Medical Center of the Johannes Gutenberg-University, Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. pautz@uni-mainz.de.
  • 2 Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • 3 Paul Klein Center for Immune Intervention, Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University, Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • 4 Department of Pharmacology, University Medical Center of the Johannes Gutenberg-University, Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
PMID: 40095032 DOI: 10.1007/s00011-025-02024-5
Abstract

Background and objective: Asthma is a chronic inflammatory disease characterized by dysregulated cytokine expression. The RNA-binding protein KSRP reduces the expression of several pro-inflammatory mediators. Therefore, we investigated whether KSRP modulates Th2-associated immune responses in vivo in an ovalbumin-induced (OVA) allergic asthma model in C57BL/6 KSRP-deficient mice (KSRP-/-).

Methods: Asthma severity in OVA-immunized wild type or KSRP-/- mice was determined by airway hyperresponsiveness (AHR), structural changes of lung tissue, and OVA-specific antibody production. Cytokine expression in bronchoalveolar lavage fluid (BALF) was measured by Cytometric Bead Array (CBA) analysis. Cellular signaling pathways involved in KSRP-mediated effects in asthma pathogenesis were analyzed in vitro in Cell Culture models using specific inhibitors.

Results: KSRP deficiency exacerbates OVA-induced allergic asthma compared to wild type mice, as indicated by increased AHR, more severe lung damage, goblet cell hyperplasia and increased OVA-specific antibody production. CBA analyses confirmed, that KSRP deficiency enhances IL-4, IL-5 and IL-13 production in BALF. The effect of KSRP on Th2-associated cytokine expression appears to be mediated by modulation of the STAT6 and NFAT signaling pathway rather than by inhibiting the stability of cytokine-encoding mRNA species.

Conclusion: Our data demonstrate that KSRP dampens Th2 immune cell activity and therefore seems to be important for the pathogenesis of Th2-mediated diseases.

Keywords

Allergic asthma; Cytokines; KSRP; Th2 cells.

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