Aorta Regulatory T Cells with a Tissue‐Specific Phenotype and Function Promote Tissue Repair through Tff1 in Abdominal Aortic Aneurysms

In addition to maintaining immune tolerance, Foxp3+ regulatory T cells (Tregs) perform specialized functions in tissue homeostasis and remodeling. However, whether Tregs in aortic aneurysms have a tissue‐specific phenotype and function is unclear. Here, a special group of Tregs that potentially inhi...

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Bibliographic Details
Published in:Advanced science 2022-03, Vol.9 (9), p.e2104338-n/a
Main Authors: Li, Jingyong, Xia, Ni, Li, Dan, Wen, Shuang, Qian, Shirui, Lu, Yuzhi, Gu, Muyang, Tang, Tingting, Jiao, Jiao, Lv, Bingjie, Nie, Shaofang, Hu, Desheng, Liao, Yuhua, Yang, Xiangping, Shi, Guoping, Cheng, Xiang
Format: Article
Language:English
Subjects:
Abdomen
abdominal aortic aneurysm
Animals
Aorta - metabolism
Aortic Aneurysm, Abdominal - genetics
Aortic Aneurysm, Abdominal - metabolism
Aortic Aneurysm, Abdominal - prevention & control
Aortic aneurysms
Apoptosis
Atherosclerosis
Coronary vessels
Extracellular matrix
Flow cytometry
Gene expression
Genotype & phenotype
Heart
Inflammation
Lymphocytes
Mice
Mice, Inbred C57BL
Phenotype
Principal components analysis
Skin
Spleen
T-Lymphocytes, Regulatory - metabolism
tissue‐specific
trefoil factor 1
Trefoil Factor-1 - genetics
Tregs
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Summary:In addition to maintaining immune tolerance, Foxp3+ regulatory T cells (Tregs) perform specialized functions in tissue homeostasis and remodeling. However, whether Tregs in aortic aneurysms have a tissue‐specific phenotype and function is unclear. Here, a special group of Tregs that potentially inhibit abdominal aortic aneurysm (AAA) progression are identified and functionally characterized. Aortic Tregs gradually increase during the process of AAA and are mainly recruited from peripheral circulation. Single‐cell TCR sequencing and bulk RNA sequencing demonstrate their unique phenotype and highly expressed trefoil factor 1 (Tff1). Foxp3cre/creTff1flox/flox mice are used to clarify the role of Tff1 in AAA, suggesting that aortic Tregs secrete Tff1 to regulate smooth muscle cell (SMC) survival. In vitro experiments confirm that Tff1 inhibits SMC apoptosis through the extracellular signal‐regulated kinase (ERK) 1/2 pathway. The findings reveal a tissue‐specific phenotype and function of aortic Tregs and may provide a promising and novel approach for the prevention of AAA. A group of Tregs with a tissue‐specific phenotype and function potentially protects abdominal aortic aneurysm progression via Tff1.
ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202104338