Objective: To investigate the regulation of hypoxia inducible factor-1 α( HIF-1α) on T lymphocyte subsets in splenocytes with collagen induced arthritis (CIA) mice by small interfering RNA (siRNA) vector. Methods: the animal model of rheumatoid arthritis was established in DBA / 1 mice were injected by bovine type Ⅱ collagen. CIA mice were injected with HIF-1α-siRNA adenovirus and negative control adenovirus, once a week for 4 weeks. The experiment was divided into control group, model group, negative control group and HIF-1α- siRNA group. The mice were killed after the experiment. The proportion of Th1cells and Th2 cells, Th17 cells and Tregs in mice spleen were detected by flow cytometry, the pathological changes of mouse ankle was observed by HE staining. Results: Compared with control group, the proportion of Th1 cells and Th17 cells in splenocytes of model group increased, the difference was statistically significant (P<0.05), the proportion of Tregs decreased, but there was no significant statistical difference, while the change of Th2 cells was not obvious. Compared with model group and negative control group, the proportion of Th1 cells and Th17 cells in splenocytes of mice in HIF-1α-siRNA group decreased, and the difference was statistically significant (P<0.05), Although Th2 cells and Tregs showed an upward trend, the difference was not statistically significant. In model group, synovial hyperplasia and a large number of lymphocytes infiltrated in the ankle joint, after HIF-1α-siRNA treated CIA mice, synovial hyperplasia and the lymphocyte infiltration of mice ankle joint was significantly reduced. Conclusion: The proportion of Th1 cells and Th17 cells in the spleen of mice were reduced, the proportion of Th2 cells and Tregs in the spleen of mice were increased, synovial hyperplasia and lymphocytes infiltration were relieved. HIF-1α-siRNA play a role in the treatment of CIA mice by regulating T cell subsets in splenocytes.
MENG Jin
,
KANG Min
,
LU Yanrong
,
GUO Yu
,
PANG Chunyan
. Regulation of hypoxia inducible factor-1 α on T cell subsets in splenocytes with collagen induced arthritis mice[J]. Journal of Baotou Medical College, 2023
, 39(5)
: 17
-21
.
DOI: 10.16833/j.cnki.jbmc.2023.05.004
[1] Klareskog L, Gregersen PK, Huizinga TW.Prevention of autoimmune rheumatic disease: state of the art and future perspectives[J].Ann Rheum Dis, 2010, 69(12): 2062-2066.
[2] Kampstra AS, van Heemst J, Moustakas AK, et al.The increased ability to present citrullinated peptides is not unique to HLA-SE molecules: arginine-to-citrulline conversion also enhances peptide affinity for HLA-DQ molecules[J].Arthritis Res Ther, 2016, 18(1): 254.
[3] Ebringer A, Rashid T.Rheumatoid arthritis is caused by a Proteus urinary tract infection[J].APMIS, 2014, 122(5): 363-368.
[4] Yu MB, Langridge WHR.The function of myeloid dendritic cells in rheumatoid arthritis[J].Rheumatol Int, 2017, 37: 1043-1051.
[5] Rao DA, Gurish MF, Marshall JL, et al.Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis[J].Nature, 2017, 542 (7639): 110-114.
[6] Prendergast CT, Patakas A, Al-Khabouri S, et al.Visualising the interaction of CD4 T cells and DCs in the evolution of inflammatory arthritis[J].Ann Rheum Dis, 2018, 77(4): 579-588.
[7] Niu Q, Huang Z, Wu X, et al.Enhanced IL-6/phosphorylated STAT3 signaling is related to the imbalance of circulating T follicular helper/T follicular regulatory cells in patients with rheumatoid arthritis[J].Arthritis Res Therapy, 2018, 20(1): 200.
[8] Aldridge J, Ekwall AH, Mark L, et al.T helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3+Th2 phenotype[J].Arthritis Res Ther, 2020, 22(1): 245.
[9] Miao J, Zhang K, Zheng Z, et al.CD147 Expressed on memory CD4+ T cells limits Th17 responses in patients with rheumatoid arthritis[J].Front Immunol, 2020, 11: 545980.
[10] Chen J, Cheng W, Li J, et al.Notch-1 and Notch-3 mediate hypoxia-induced activation of synovial fibroblasts in rheumatoid arthritis[J]. Arthritis Rheumatol, 2021, 73(10): 1810-1819.
[11] Feng ZT, Yang T, Hou XQ, et al.Sinomenine mitigates collagen-induced arthritis mice by inhibiting angiogenesis[J].Biomed Pharmacother, 2019, 113: 108759.
[12] Liu X, Guo R, Huo S, et al.CaP-based anti-inflammatory HIF-1α siRNA-encapsulating nanoparticle for rheumatoid arthritis therapy[J].J Control Release, 2022, 343: 314-325.
[13] Hu F, Mu R, Zhu J, et al.Hypoxia and hypoxia-inducible factor-1α provoke toll-like receptor signalling-induced inflammation in rheumatoid arthritis[J].Ann Rheum Dis, 2014, 73(5): 928-936.
[14] Hu F, Liu H, Xu L, et al.Hypoxia-inducible factor-1α perpetuates synovial fibroblast interactions with T cells and B cells in rheumatoid arthritis[J].Eur J Immunol, 2016, 46(3): 742-751.
[15] Liu J, Hong X, Lin D, et al.Artesunate influences Th17/Treg lymphocyte balance by modulating Treg apoptosis and Th17 proliferation in a murine model of rheumatoid arthritis[J].Exp Ther Med, 2017, 13: 2267-2273.
[16] Niu Q, Cai B, Huang ZC, et al.Disturbed Th17/Treg balance in patients with rheumatoid arthritis[J].Rheumatol Int, 2012, 32(9): 2731-2736.
[17] Ye H, Fu D, Fang X, et al.Casein Kinase Ⅱ exacerbates rheumatoid arthritis via promoting Th1 and Th17 cell inflammatory responses[J].Expert Opin Ther Targets, 2021, 25(11): 1017-1024.
