What does this research mean for the field?

Glucocorticoid treatment during acute lung injury alters the phenotypes and transcriptomic profiles of regulatory and conventional T cells, significantly decreasing the accumulation of activated T cells in the lungs and spleen. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to characterize how glucocorticoids affect lymphocyte responses, particularly regulatory T cells, in the context of acute lung injury.

May 20, 2026

A33-04 Glucocorticoid Effects on Lymphocyte Dynamics in Acute Lung Injury

Key Points

This research aims to characterize how glucocorticoids affect lymphocyte responses, particularly regulatory T cells, in the context of acute lung injury.
Foxp3 DTR mice were used with intratracheal lipopolysaccharide administration to establish ALI.
Mice were treated with intraperitoneal dexamethasone or phosphate-buffered saline from days 1-5 post-injury.
Flow cytometric immunophenotyping and bulk RNA sequencing were conducted on samples collected at day 7.
DEX-treated mice showed less weight loss and better lung function on day 4 post-LPS.
CD3+ T cells and activated CD44+ CD4+ T cells were significantly reduced in the lungs of DEX-treated mice compared to PBS-treated mice.
Transcriptomic differences were noted between Tconv cells, Treg cells, and CD8 T cells from DEX versus PBS-treated mice.

Abstract

Abstract Rationale Forkhead box protein 3 (Foxp3)-expressing regulatory T cells (Tregs) are an important immune cell type involved in the resolution of acute lung injury (ALI). Glucocorticoids (GCs) are a class of broad-acting anti-inflammatory drugs that are used in the treatment of many respiratory diseases. GC modulation of lymphocyte responses during ALI and their impact on Treg cells is not well characterized. Methods Foxp3 DTR mice were administered lipopolysaccharide (LPS) via intratracheal instillation to establish ALI. From days 1-5 post-injury, mice were treated twice daily with intraperitoneal dexamethasone (DEX) or phosphate-buffered saline (PBS). Body weight was recorded daily, and pulse oximetry was performed on days 2-6 to assess lung function. Spleen, lung, and bronchoalveolar lavage (BAL) samples were collected during resolution (day 7) for flow cytometric immunophenotyping. Splenic CD4+Foxp3- (Tconv), CD4+Foxp3 + (Treg), and CD8+ T cells were isolated by fluorescence-activated cell sorting (FACS) for bulk RNA sequencing. Results DEX-treated mice showed a trend toward lower percentage weight loss and better lung function at peak injury on day 4 post-LPS. Spleens isolated from DEX-treated mice weighed significantly less than spleens from PBS-treated mice. Flow cytometric experiments revealed that the percentage of CD45+ immune cells was decreased significantly in the lung and did not differ significantly in BAL from DEX-treated mice compared to PBS-treated mice. CD3+ T cells were significantly decreased in the lungs of DEX-treated mice compared to PBS-treated mice. Within the T cell compartment, the percentage of activated CD44+ CD4+ T cells was significantly decreased in the spleen and lung of Dex-treated mice compared to PBS-treated mice. The percentage of CD44+ Treg cells was also significantly decreased in the lungs of Dex-treated mice. Bulk RNA sequencing revealed broad transcriptomic differences between Tconv cells, Treg cells, and CD8 T cells isolated from the spleens of Dex versus PBS-treated mice. Conclusion DEX treatment altered Treg and Tconv phenotypes during ALI. Next steps include depletion of Tregs by administering diphtheria toxin (DT) to Foxp3DTR mice to determine the Treg-dependent and -independent mechanisms through which glucocorticoids act. This abstract is funded by: NIH 1R01HL173765-01A1

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A33-04 Glucocorticoid Effects on Lymphocyte Dynamics in Acute Lung Injury

Key Points

Abstract

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