Transcriptomic analysis identifies STAT1 as a potential key transcriptional regulator of T-cell dysfunction in AIHA
- 1Department of Hematology, The Second Affiliated Hospital of Nanchang University
- 2Jiangxi Provincial Key Laboratory of Hematological Diseases (2024SSY06052)
- 3Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
Abstract
Background: Autoimmune hemolytic anemia (AIHA) is characterized by antibody-mediated red blood cell destruction. T-cell dysfunction is implicated in its pathogenesis, but the underlying transcriptional mechanisms remain poorly understood.
Methods: We analyzed peripheral CD4+ and CD8+ T cells from patients with primary warm AIHA and healthy controls by flow cytometry and RNA sequencing. Transcription factor enrichment, ChEA3, an external AIHA Treg dataset, immune-function scores, and clinical correlations were examined. LDH was measured after ex vivo treatment with resveratrol or fludarabine. In an AIHA mouse model, we assessed LDH, spleen weight, erythrocyte-bound IgG, and peripheral T-cell STAT1 and pSTAT1 fluorescence after treatment with resveratrol or fludarabine.
Results: The AIHA group had a higher proportion of peripheral CD8+ T cells and altered CD4+ and CD8+ T cell transcriptional profiles. Transcription factor analysis identified STAT1 as a shared regulatory candidate in both CD4+ and CD8+ T cells. In the mouse experiment, LDH, spleen weight, erythrocyte-bound IgG fluorescence, and peripheral CD4+ and CD8+ T cell STAT1 and pSTAT1 fluorescence were higher in the AIHA group than in controls and lower in the resveratrol and fludarabine groups than in untreated AIHA mice.
Conclusion: Our study identifies STAT1 as a potential transcriptional regulator associated with T-cell dysfunction and hemolytic activity in AIHA. These findings support further investigation of STAT1-associated signaling as a possible therapeutic target.
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BibTeX
@article{xu2026transcriptomic,
title = {{Transcriptomic analysis identifies STAT1 as a potential key transcriptional regulator of T-cell dysfunction in AIHA}},
author = {Jing Xu and Linhui Hu and Haixiang Wan and Yixin Yan and Qingming Wang and XueXin Cheng and Zhenjiang Li},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1896404},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1896404/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transcriptomic analysis identifies STAT1 as a potential key transcriptional regulator of T-cell dysfunction in AIHA
AU - Jing Xu
AU - Linhui Hu
AU - Haixiang Wan
AU - Yixin Yan
AU - Qingming Wang
AU - XueXin Cheng
AU - Zhenjiang Li
PY - 2026
DA - 2026/10/23
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1896404
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1896404/full
AB - Background: Autoimmune hemolytic anemia (AIHA) is characterized by antibody-mediated red blood cell destruction. T-cell dysfunction is implicated in its pathogenesis, but the underlying transcriptional mechanisms remain poorly understood. Methods: We analyzed peripheral CD4+ and CD8+ T cells from patients with primary warm AIHA and healthy controls by flow cytometry and RNA sequencing. Transcription factor enrichment, ChEA3, an external AIHA Treg dataset, immune-function scores, and clinical correlations were examined. LDH was measured after ex vivo treatment with resveratrol or fludarabine. In an AIHA mouse model, we assessed LDH, spleen weight, erythrocyte-bound IgG, and peripheral T-cell STAT1 and pSTAT1 fluorescence after treatment with resveratrol or fludarabine. Results: The AIHA group had a higher proportion of peripheral CD8+ T cells and altered CD4+ and CD8+ T cell transcriptional profiles. Transcription factor analysis identified STAT1 as a shared regulatory candidate in both CD4+ and CD8+ T cells. In the mouse experiment, LDH, spleen weight, erythrocyte-bound IgG fluorescence, and peripheral CD4+ and CD8+ T cell STAT1 and pSTAT1 fluorescence were higher in the AIHA group than in controls and lower in the resveratrol and fludarabine groups than in untreated AIHA mice. Conclusion: Our study identifies STAT1 as a potential transcriptional regulator associated with T-cell dysfunction and hemolytic activity in AIHA. These findings support further investigation of STAT1-associated signaling as a possible therapeutic target.
SN - 1664-3224
ER -