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Abstract: TH-PO944

Decreased TFH, GCB, PC, and Increased TFR Cell Frequencies in Spleen of Mice Fed with a Glutamine-Free Diet

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1500 Health Maintenance, Nutrition, and Metabolism


  • Yang, Li-Shiuan, Chang Gung University, Taoyuan, Taiwan
  • Tsai, Chung Ying, Chang Gung Memorial Hospital Linkou, Taoyuan, Taiwan
  • Yang, Huang-Yu, Chang Gung University, Taoyuan, Taiwan

We investigated the effects of a glutamine (Gln)-free diet (GFD) and the Gln analog 6-Diazo-5-oxo-L-norleucine (DON) on immune cell populations in mice. Specifically, T follicular helper cells (TFH), T follicular regulatory cells (TFR), germinal center B cells (GCB), and plasma cells (PC) in spleen. Additionally, we assessed the impact of CD4-specific GLS1 deficiency (KO) on TFH frequency and evaluated the therapeutic effects of GFD and DON in a lupus mouse model.


Animal and Groups:
Eight-week-old WT B6 male mice were divided into four groups: chow+PBS or DON, GFD+PBS or DON. After 2-week treatment, mice immunized with LPS-OVA Alum and sacrificed 7.5 days later.
Cell Frequencies:
Flow cytometry was performed to determine the TFH, TFR, GCB, and PC frequencies.
CD4 T cell-GLS1 KO:
GLS1f/fCD4-cre0/0, Tg/0 mice were utilized.
Lupus Mouse Model and Therapeutic Interventions:
1. Five- to six-month-old MRL/lpr mice were used and divided into two groups: GFD-fed mice and DON-treated mice.
2. Cell frequencies in spleen and kidney were determined.
3. Serum anti-ANA, anti-dsDNA, and IgG1 antibodies were measured.
4. Kidney sections were examined for anti-glomerulus IgG deposition.


Effects of GFD and DON on T and B Cell Frequencies
1. Mice treated with chow+DON, GFD+PBS or DON exhibited decreased TFH, GCB, and PC frequencies compared to chow+PBS mice.
2. GFD+PBS treatment led to the highest frequency of TFR cells among all groups.
CD4 T Cell-GLS1 KO and TFH Frequency
CD4 T cells with GLS1 KO showed a primary reduction in TFH frequency.
Therapeutic Effects of GFD and DON in Lupus Mice
1. Mice with GFD or DON exhibited amelioration of lupus symptoms.
2. TFH and PC frequencies in spleen were reduced in GFD-fed mice.
3. GFD and DON treatments resulted in lower level of serum anti-ANA, anti-dsDNA, and IgG1 antibodies.
4. DON treatment significantly reduced the total frequency of kidney infiltrated lymphocytes.


Our findings demonstrate that a GFD can decrease TFH, GCB, and PC cell frequencies, while increasing TFR cell frequency in spleen of mice. CD4 T cell-specific GLS1 KO primarily reduces TFH frequency. Furthermore, both GFD and DON show therapeutic effects in ameliorating lupus symptoms in the MRL/lpr mouse model. These results suggest the potential of manipulating Gln metabolism as a therapeutic strategy for autoimmune diseases like lupus.


  • Private Foundation Support