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Abstract: FR-PO404

Characterization of TRIM72 Immune Modulatory Functions

Session Information

Category: Development‚ Stem Cells‚ and Regenerative Medicine

  • 500 Development‚ Stem Cells‚ and Regenerative Medicine

Authors

  • Duann, Pu, The Ohio State University, Columbus, Ohio, United States
  • Rovin, Brad H., The Ohio State University, Columbus, Ohio, United States
  • Lin, Pei-Hui, The Ohio State University, Columbus, Ohio, United States
Background

TRIM72 (MG53) is a myokine that appears to confer protection to the kidney in ischemia-reperfusion (I/R) injury and kidney fibrosis. We recently discovered the functional duality of TRIM72 as a membrane repair protein and immune system regulator in kidney protection. We conducted experiments to identify whether TRIM72 is expressed within the immune system, and further investigated whether TRIM72 affected inflammatory cytokine profiles.

Methods

Spleen and bone marrow from wildtype (mg53+/+) or trim72-null (mg53-/-) age and gender-matched young adult mice were harvested. Thymus from pups at postnatal days 8, 18, and 24 were harvested and separated into thymic stroma and thymocytes. Tissue TRIM72 expression was analyzed by western blot and quantitative RT-PCR (qRT-PCR). Thymocyte and splenocyte immune phenotypes were further analyzed with anti-CD3, -CD4, -CD25 and -FoxP3 flow cytometry. In addition, we profiled serum from wildtype and trim72-null mice for pro-inflammatory cytokines using the V-PLEX Plus pro-inflammatory panel 1 (MSD company). The V-PLEX measures 10 cytokines (INFγ, IL-1b, IL-2, IL-4, IL-5, IL-6, CXCL1, IL-10, IL-12p70 and TNFα).

Results

We detected TRIM72 expression in thymus, spleen and bone marrow. TRIM72 is expressed in the thymic stroma, a tissue that regulates T cell tolerance early in life. Thymic expression was moderate, roughly 3% that of skeletal muscle. Wildtype pups had a higher proportion of thymocytes that were CD4+, CD25+, FoxP3+ (Tregs, 4.71%) than thymocytes from trim72-null pups (3.27%, p* <0.05). Bone marrow and spleen expressed lower levels of TRIM72 than the thymus. Of the 10 cytokines examined from serum, CXCL1, IL-2, IL-5, IL-10 and TNFα were significantly elevated in trim72-null mice.

Conclusion

TRIM72 may facilitate the development of thymic Tregs, and provide basal inhibition of proinflammatory cytokines. Taken together, these findings suggest TRIM72 has anti-inflammatory and pro-tolerogenic immunomodulatory functions.

Funding

  • NIDDK Support