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Journal of Peking University (Health Sciences) ›› 2024, Vol. 56 ›› Issue (3): 519-525. doi: 10.19723/j.issn.1671-167X.2024.03.020

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Regulatory effect of lactate on peripheral blood CD4+ T cell subsets in patients with rheumatoid arthritis

Huina HUANG1,Jing ZHAO2,Xiangge ZHAO1,Ziran BAI1,Xia LI1,Guan WANG1,*()   

  1. 1. Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, Liaoning, China
    2. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China
  • Received:2023-10-24 Online:2024-06-18 Published:2024-06-12
  • Contact: Guan WANG E-mail:guanwang1988@dmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(82071834);the National Natural Science Foundation of China(82271839);the National Natural Science Foundation of China(82101896)

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Abstract:

Objective: To investigate the serum lactate level in patients with rheumatoid arthritis (RA) and its relationship with disease activity, and to analyze the effect of sodium lactate on the activation of CD4+ T cells, the ability of secreting cytokines and CD4+T cell subsets in peripheral blood of the RA patients. Methods: The peripheral blood of healthy controls (HC) and RA patients was collected, and the content of lactate in the supernatant was detected by lactate detection kit, the correlation between the content of lactate and the disease score of the RA patients was analyzed; the activation level of CD4+ T cells, the proportion of CD4+ T cell subsets and the cytokines secreted by CD4+ T cells in peripheral blood of all the RA patients were detected by flow cytometry after being stimulated with sodium lactate. Results: The serum lactate level in the RA patients (n=66) was significantly higher than that in the HC (n=60, P < 0.001), and there was a certain correlation with disease activity score in 28 joints (DAS28)-C-reactive protein (CRP) (r=0.273, P=0.029), The levels of rheumatoid factor [RF, 197.50 (26.03, 783.00) IU/mL vs. 29.30 (0.00, 102.60) IU/mL, P < 0.01], CRP [37.40 (11.30, 72.60) mg/L vs. 5.83 (2.36, 12.45) mg/L, P < 0.001], were increased in patients with the lactate concentration greater than 5 mmol/L were significantly higher than those in patients with the lactate concentration less than or equal 5 mmol/L, however, there was no significant difference in the expression of erythrocyte sedimentation rate [ESR, 42.00 (19.00, 77.00) mm/h vs. 25.00 (12.50, 45.50) mm/h, P>0.05] and anti-cyclic citrullinated peptied (CCP) antibody [82.35 (17.70, 137.00) RU/mL vs. 68.60 (25.95, 119.70) RU/mL, P>0.05]. Compared with the control group, the expression of PD-1 (46.15%±8.54% vs. 41.67%±9.98%, P < 0.001), inducible costimulatory molecule (ICOS, 5.77%±8.60% vs. 18.65%±7.94%, P < 0.01) and CD25 (25.89%±5.80% vs. 22.25%±4.59%, P < 0.01) on the surface of CD4+ T cells in the RA patients treated with sodium lactate was significantly increased. Compared with the control group, the proportion of Th17 (4.62%±1.74% vs. 2.93%±1.92%, P < 0.05) and Tph (28.02%±6.28% vs. 20.32%±5.82%, P < 0.01) cells in CD4+T cells of the RA patients in the sodium lactate treatment group increased. Compared with the control group, the expression of IL-21 (5.73%±1.59% vs. 4.75%±1.71%, P < 0.05) in CD4+T cells was up-regulated in the RA patients treated with sodium lactate. Conclusion: The level of serum lactate in RA patients is increased, which promotes the activation of CD4+T cells and the secretion of IL-21, and up-regulates the proportion of Th17 and Tph cells in the RA patients.

Key words: Rheumatoid arthritis, Lactate, CD4+T cell, Peripheral helper T (Tph) cell

CLC Number: 

  • R593.22

Table 1

The basic characteristics of RA patients and HC"

Items RA patients (n=66) HC (n=60)
Age/years, M (P25, P75) 60.00 (50.75, 67.25) 55.00 (41.00, 57.00)
Gender, n(%)
   Male 14 (21.2) 16 (26.6)
   Female 52 (78.8) 44 (73.4)
Course of disease/months, M (P25, P75) 24.00 (8.00, 96.00), n=63
RF/(IU/mL), M (P25, P75) 79.80 (0.00, 544.00), n=65
anti-CCP/(RU/mL), M (P25, P75) 73.40 (22.80, 130.30), n=28
CRP/(mg/L), M (P25, P75) 14.40 (5.73, 49.65), n=64
ESR/(mm/h), M (P25, P75) 33.00 (16.00, 71.50)， n=64
DAS28-CRP, M (P25, P75) 4.88 (3.92, 6.09)， n=64

Figure 1

Serum lactate levels in HC and patients with RA and their correlation with disease activity HC, healthy control; RA, rheumatoid arthritis; L, low disease activity group (n=21); M, medium disease activity group (n=21); H, high disease activity group (n=22); RF, rheumatoid factor; CCP, cyclic citrullinated peptied; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; a, lactate≤5 mmol/L; b, lactate > 5 mmol/L. # P < 0.01, △ P < 0.001, ☆ P < 0.000 1; ns, no significance."

Figure 2

Effect of sodium lactate on CD4+ T cell activity in patients with rheumatoid arthritis (RA) A, schematic diagram of the flow cytometry loop gate; B to F, expression of activation markers CD69, PD-1, inducible costimulatory molecule (ICOS), CD25 and CD84 on the surface of CD4+ T cells, after peripheral blood mononuclear cell (PBMC) from RA patients were stimulated with sodium lactate for 72 hours. Con, control group; La, sodium lactate stimulation group. # P < 0.01, △ P < 0.001; ns, no significance."

Figure 3

Effect of sodium lactate on CD4+T cell subsets in patients with rheumatoid arthritis (RA) A to E, Expression of IFN-γ, IL-4, IL-17A, Foxp3, PD-1 and CXCR5 in CD4+ T cells, after 72 hours of sodium lactate stimulation of peripheral blood PBMC from RA patients. IFN-γ represents Th1 cells; IL-4 represents Th2 cells; IL-17A represents Th17 cells; Foxp3 represents Treg cells; PD-1+CXCR5+ represents Tfh cells; PD-1+CXCR5- represents Tph cells. Con, control group; La, sodium lactate stimulation group. * P < 0.05, # P < 0.01; ns, no significance."

Figure 4

Effect of sodium lactate on cytokine secretion by CD4+T cells in patients with rheumatoid arthritis (RA) A, expression of IL-21 and CXCL13 in CD4+ T cells, after 72 hours of sodium lactate stimulation of peripheral blood peripheral blood mononuclear cell (PBMC) from RA patients. Con, control group; La, sodium lactate stimulation group. * P < 0.05; ns, no significance."

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