Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00056)
Name
Systemic lupus erythematosus
ICD
ICD-11: 4A40
Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 13 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-1/13 (IFNA1; IFNA13) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

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Response regulation IFN- ( IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-2 (IFNA2) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-4 (IFNA4) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-5 (IFNA5) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-6 (IFNA6) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-7 (IFNA7) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-8 (IFNA8) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 8 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-10 (IFNA10) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 9 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-1/13 (IFNA1; IFNA13) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 10 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-14 (IFNA14) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 11 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-16 (IFNA16) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 12 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-17 (IFNA17) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
Experiment 13 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Systemic lupus erythematosus [ICD-11: 4A40]
Responsed Regulator Interferon alpha-21 (IFNA21) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPBMCs (Human peripheral blood mononuclear cells)
In Vivo Model
In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age.

    Click to Show/Hide
Response regulation IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations.
References
Ref 1 Glutathione peroxidase 4-regulated neutrophil ferroptosis induces systemic autoimmunity. Nat Immunol. 2021 Sep;22(9):1107-1117. doi: 10.1038/s41590-021-00993-3. Epub 2021 Aug 12.