FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity
Background: Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease, which is accompanied by liver damage. However, it remains unknown whether liver damage is associated with SLE progression. Method: ology: HepG2 and L-02 cells were stimulated with cytokines, and FGL1 mRNA and protein...
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Elsevier
2023-10-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023080143 |
| _version_ | 1797646438208897024 |
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| author | Kang Chen Xingyu Li Yuqi Shang Daxiang Chen Siying Qu Jinxian Shu Mei Zhang Zhiying Wang Jinmei Huang Minhao Wu Siqi Ming Yongjian Wu |
| author_facet | Kang Chen Xingyu Li Yuqi Shang Daxiang Chen Siying Qu Jinxian Shu Mei Zhang Zhiying Wang Jinmei Huang Minhao Wu Siqi Ming Yongjian Wu |
| author_sort | Kang Chen |
| collection | DOAJ |
| description | Background: Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease, which is accompanied by liver damage. However, it remains unknown whether liver damage is associated with SLE progression. Method: ology: HepG2 and L-02 cells were stimulated with cytokines, and FGL1 mRNA and protein expression levels were determined using Real-time PCR and ELISA, respectively. Regulatory T cells (Treg) isolated from healthy individuals as well as patients with SLE and SLE and liver damage (SLE-LD) were cultured with autologous effector CD4+T cells in the presence of a functional antibody or isotype control. The expression levels of LAG3, CD25, PD-1, CXCR5, ICOS and OX40 were evaluated by flow cytometry. FGL1, IL-10, IL-17a and IL-21 levels in serum or culture supernatants were quantified by ELISA. Results: Patients with SLE-LD exhibits higher disease activity indices and anti-dsDNA antibody levels. Importantly, fibrinogen-like protein 1 (FGL1), a key factor released from the injured liver, is up-regulated in patients with SLE-LD and is associated with disease activity. FGL1 expression is induced by the inflammatory cytokine IL-6 signaling in hepatocytes. Higher expression of the FGL1 receptor lymphocyte activation gene 3 (LAG3) is detected in Treg cells from patients with SLE-LD. The FGL1-LAG3 signaling axis inhibits Treg cell proliferation and impairs the suppressive activity of Treg cells by limiting IL-10 secretion. Furthermore, FGL1-LAG3 signaling promotes the production of pathogenic IL-17a and IL-21 by CD4+T cells by reducing IL-10 level produced by Treg in patients with SLE. Conclusions: The FGL1-LAG3 signal axis is a key mechanism that subverts the suppressive function of Treg cells. This may provide a new therapeutic target for SLE and SLE-induced liver damage. |
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| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-11T15:02:37Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-3dee903ebb784cc5a12b6589e4df69cf2023-10-30T06:07:29ZengElsevierHeliyon2405-84402023-10-01910e20806FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activityKang Chen0Xingyu Li1Yuqi Shang2Daxiang Chen3Siying Qu4Jinxian Shu5Mei Zhang6Zhiying Wang7Jinmei Huang8Minhao Wu9Siqi Ming10Yongjian Wu11Department of Laboratory Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong Province, 528403, ChinaCenter for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China; Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Zhuhai, Guangdong Province, 519015, ChinaDepartment of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, ChinaDepartment of Laboratory Medicine, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510091, ChinaDepartment of Clinical Laboratory, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, The Second People's Hospital of Zhuhai, Zhuhai, Guangdong, 519020, ChinaDepartment of pharmacy, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, ChinaThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong Province, 511518, ChinaDepartment of Laboratory Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong Province, 528403, ChinaDepartment of Laboratory Medicine, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510091, China; Corresponding author.Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China; Corresponding author.Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Zhuhai, Guangdong Province, 519015, China; Corresponding author.Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China; Corresponding author.Background: Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease, which is accompanied by liver damage. However, it remains unknown whether liver damage is associated with SLE progression. Method: ology: HepG2 and L-02 cells were stimulated with cytokines, and FGL1 mRNA and protein expression levels were determined using Real-time PCR and ELISA, respectively. Regulatory T cells (Treg) isolated from healthy individuals as well as patients with SLE and SLE and liver damage (SLE-LD) were cultured with autologous effector CD4+T cells in the presence of a functional antibody or isotype control. The expression levels of LAG3, CD25, PD-1, CXCR5, ICOS and OX40 were evaluated by flow cytometry. FGL1, IL-10, IL-17a and IL-21 levels in serum or culture supernatants were quantified by ELISA. Results: Patients with SLE-LD exhibits higher disease activity indices and anti-dsDNA antibody levels. Importantly, fibrinogen-like protein 1 (FGL1), a key factor released from the injured liver, is up-regulated in patients with SLE-LD and is associated with disease activity. FGL1 expression is induced by the inflammatory cytokine IL-6 signaling in hepatocytes. Higher expression of the FGL1 receptor lymphocyte activation gene 3 (LAG3) is detected in Treg cells from patients with SLE-LD. The FGL1-LAG3 signaling axis inhibits Treg cell proliferation and impairs the suppressive activity of Treg cells by limiting IL-10 secretion. Furthermore, FGL1-LAG3 signaling promotes the production of pathogenic IL-17a and IL-21 by CD4+T cells by reducing IL-10 level produced by Treg in patients with SLE. Conclusions: The FGL1-LAG3 signal axis is a key mechanism that subverts the suppressive function of Treg cells. This may provide a new therapeutic target for SLE and SLE-induced liver damage.http://www.sciencedirect.com/science/article/pii/S2405844023080143Systemic lupus erythematosusRegulatory T cellLymphocyte-activation protein 3Fibrinogen-like protein 1 |
| spellingShingle | Kang Chen Xingyu Li Yuqi Shang Daxiang Chen Siying Qu Jinxian Shu Mei Zhang Zhiying Wang Jinmei Huang Minhao Wu Siqi Ming Yongjian Wu FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity Heliyon Systemic lupus erythematosus Regulatory T cell Lymphocyte-activation protein 3 Fibrinogen-like protein 1 |
| title | FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity |
| title_full | FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity |
| title_fullStr | FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity |
| title_full_unstemmed | FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity |
| title_short | FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity |
| title_sort | fgl1 lag3 axis impairs il 10 producing regulatory t cells associated with systemic lupus erythematosus disease activity |
| topic | Systemic lupus erythematosus Regulatory T cell Lymphocyte-activation protein 3 Fibrinogen-like protein 1 |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023080143 |
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