Hao Wang1,2, Guodong Wei1,2, Shuai Cheng1,2, Ding Wang1,2, Ju Ma1,2, Shijie Xin3,4. 1. Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, China. 2. Liaoning Provincial Key Laboratory of Aneurysm Etiology and Prevention, Shenyang, China. 3. Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, China, sjxin@cmu.edu.cn. 4. Liaoning Provincial Key Laboratory of Aneurysm Etiology and Prevention, Shenyang, China, sjxin@cmu.edu.cn.
Abstract
INTRODUCTION: CD4-positive T lymphocytes (CD4 cells) play a significant role in human abdominal aortic aneurysm (AAA). However, we know little about the role of the different CD4 subtypes. OBJECTIVE: We aimed to discover the circulatory CD4 phenotypic marker profile and the roles of the newly found T helper cell 9 (Th9) and follicular helper T cells (Tfh) and that of inflammasomes in CD4 cells from AAA patients. METHODS: We extracted CD4 cells from 30 AAA patients and 21 age-matched controls. Phenotype-specific transcription factors (TFs) and inflammasomes were analyzed with qRT-PCR. RESULTS: Th17-, Th1-, Th9-, and Tfh-specific TFs and inflammasome components NLRP1 (NLR family pyrin domain-containing 1), NLRP3, NLRC4, AIM2 (absent in melanoma 2), PYCARD (apoptosis speck-like protein containing a CARD), and CASP1 (caspase 1) were upregulated, and T regulatory cell- and Th2-specific TFs were downregulated in the patients' peripheral blood CD4 cells. Homocysteine was involved in Tfh and Th17 imbalance by AIM2 and NLRP1 inflammasome upregulation. Blood total cholesterol level correlated positively with NLRP1 expression, and blood low-density lipoprotein level correlated negatively with FOXP3 expression. CONCLUSIONS: Inflammasome-induced CD4 cell imbalance was involved in AAA. We thought that AAA might be a consequence of synergism between systemic immune imbalance and local autoimmunity.
INTRODUCTION:CD4-positive T lymphocytes (CD4 cells) play a significant role in humanabdominal aortic aneurysm (AAA). However, we know little about the role of the different CD4 subtypes. OBJECTIVE: We aimed to discover the circulatory CD4 phenotypic marker profile and the roles of the newly found T helper cell 9 (Th9) and follicular helper T cells (Tfh) and that of inflammasomes in CD4 cells from AAA patients. METHODS: We extracted CD4 cells from 30 AAA patients and 21 age-matched controls. Phenotype-specific transcription factors (TFs) and inflammasomes were analyzed with qRT-PCR. RESULTS: Th17-, Th1-, Th9-, and Tfh-specific TFs and inflammasome components NLRP1 (NLR family pyrin domain-containing 1), NLRP3, NLRC4, AIM2 (absent in melanoma 2), PYCARD (apoptosis speck-like protein containing a CARD), and CASP1 (caspase 1) were upregulated, and T regulatory cell- and Th2-specific TFs were downregulated in the patients' peripheral blood CD4 cells. Homocysteine was involved in Tfh and Th17 imbalance by AIM2 and NLRP1 inflammasome upregulation. Blood total cholesterol level correlated positively with NLRP1 expression, and blood low-density lipoprotein level correlated negatively with FOXP3 expression. CONCLUSIONS: Inflammasome-induced CD4 cell imbalance was involved in AAA. We thought that AAA might be a consequence of synergism between systemic immune imbalance and local autoimmunity.