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Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation

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Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation. / Esposito, Marianna; Ruffini, Francesca; Bellone, Matteo; Gagliani, Nicola; Battaglia, Manuela; Martino, Gianvito; Furlan, Roberto.

In: J NEUROIMMUNOL, Vol. 220, No. 1-2, 30.03.2010, p. 52-63.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Esposito, M, Ruffini, F, Bellone, M, Gagliani, N, Battaglia, M, Martino, G & Furlan, R 2010, 'Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation', J NEUROIMMUNOL, vol. 220, no. 1-2, pp. 52-63. https://doi.org/10.1016/j.jneuroim.2010.01.001

APA

Esposito, M., Ruffini, F., Bellone, M., Gagliani, N., Battaglia, M., Martino, G., & Furlan, R. (2010). Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation. J NEUROIMMUNOL, 220(1-2), 52-63. https://doi.org/10.1016/j.jneuroim.2010.01.001

Vancouver

Esposito M, Ruffini F, Bellone M, Gagliani N, Battaglia M, Martino G et al. Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation. J NEUROIMMUNOL. 2010 Mar 30;220(1-2):52-63. https://doi.org/10.1016/j.jneuroim.2010.01.001

Bibtex

@article{b21e2b26e3264095adac7d4cb0545ea8,
title = "Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation",
abstract = "Rapamycin is an oral immunosuppressant drug previously reported to efficiently induce naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T ((n)T(reg)) cells re-establishing long-term immune self-tolerance in autoimmune diseases. We investigated the effect of rapamycin administration to SJL/j mice affected by PLP(139-151)-induced relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE). We found that oral or intraperitoneal treatment at the peak of disease or at the end of the first clinical attack, dramatically ameliorated the clinical course of RR-EAE. Treatment suspension resulted in early reappearance of disease. Clinical response was associated with reduced central nervous system demyelination and axonal loss. Rapamycin induced suppression of IFN-gamma, and IL-17 release from antigen-specific T cells in peripheral lymphoid organs. While CD4(+)FoxP3(+) cells were unaffected, we observed disappearance of CD4(+)CD45RB(high) effector T (T(eff)) cells and selective expansion of T(reg) cells bearing the CD4(+)CD45RB(low)FoxP3(+)CD25(+)CD103(+) extended phenotype. Finally, the dual action of rapamycin on both T(eff) and T(reg) cells resulted in modulation of their ratio that closely paralleled disease course. Our data show that rapamycin inhibits RR-EAE, provide evidence for the immunological mechanisms, and indicate this compound as a potential candidate for the treatment of multiple sclerosis.",
keywords = "Animals, Antigens, Differentiation, T-Lymphocyte, Antigens, Surface, Disease Models, Animal, Drug Administration Routes, Encephalomyelitis, Autoimmune, Experimental, Female, Immune Tolerance, Immunosuppressive Agents, Interferon-gamma, Interleukin-17, Mice, Multiple Sclerosis, Relapsing-Remitting, Myelin Proteolipid Protein, Peptide Fragments, Phenotype, Secondary Prevention, Sirolimus, T-Lymphocytes, Regulatory, Treatment Outcome, Journal Article, Research Support, Non-U.S. Gov't",
author = "Marianna Esposito and Francesca Ruffini and Matteo Bellone and Nicola Gagliani and Manuela Battaglia and Gianvito Martino and Roberto Furlan",
note = "Copyright 2010 Elsevier B.V. All rights reserved.",
year = "2010",
month = mar,
day = "30",
doi = "10.1016/j.jneuroim.2010.01.001",
language = "English",
volume = "220",
pages = "52--63",
journal = "J NEUROIMMUNOL",
issn = "0165-5728",
publisher = "Elsevier",
number = "1-2",

}

RIS

TY - JOUR

T1 - Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation

AU - Esposito, Marianna

AU - Ruffini, Francesca

AU - Bellone, Matteo

AU - Gagliani, Nicola

AU - Battaglia, Manuela

AU - Martino, Gianvito

AU - Furlan, Roberto

N1 - Copyright 2010 Elsevier B.V. All rights reserved.

PY - 2010/3/30

Y1 - 2010/3/30

N2 - Rapamycin is an oral immunosuppressant drug previously reported to efficiently induce naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T ((n)T(reg)) cells re-establishing long-term immune self-tolerance in autoimmune diseases. We investigated the effect of rapamycin administration to SJL/j mice affected by PLP(139-151)-induced relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE). We found that oral or intraperitoneal treatment at the peak of disease or at the end of the first clinical attack, dramatically ameliorated the clinical course of RR-EAE. Treatment suspension resulted in early reappearance of disease. Clinical response was associated with reduced central nervous system demyelination and axonal loss. Rapamycin induced suppression of IFN-gamma, and IL-17 release from antigen-specific T cells in peripheral lymphoid organs. While CD4(+)FoxP3(+) cells were unaffected, we observed disappearance of CD4(+)CD45RB(high) effector T (T(eff)) cells and selective expansion of T(reg) cells bearing the CD4(+)CD45RB(low)FoxP3(+)CD25(+)CD103(+) extended phenotype. Finally, the dual action of rapamycin on both T(eff) and T(reg) cells resulted in modulation of their ratio that closely paralleled disease course. Our data show that rapamycin inhibits RR-EAE, provide evidence for the immunological mechanisms, and indicate this compound as a potential candidate for the treatment of multiple sclerosis.

AB - Rapamycin is an oral immunosuppressant drug previously reported to efficiently induce naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T ((n)T(reg)) cells re-establishing long-term immune self-tolerance in autoimmune diseases. We investigated the effect of rapamycin administration to SJL/j mice affected by PLP(139-151)-induced relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE). We found that oral or intraperitoneal treatment at the peak of disease or at the end of the first clinical attack, dramatically ameliorated the clinical course of RR-EAE. Treatment suspension resulted in early reappearance of disease. Clinical response was associated with reduced central nervous system demyelination and axonal loss. Rapamycin induced suppression of IFN-gamma, and IL-17 release from antigen-specific T cells in peripheral lymphoid organs. While CD4(+)FoxP3(+) cells were unaffected, we observed disappearance of CD4(+)CD45RB(high) effector T (T(eff)) cells and selective expansion of T(reg) cells bearing the CD4(+)CD45RB(low)FoxP3(+)CD25(+)CD103(+) extended phenotype. Finally, the dual action of rapamycin on both T(eff) and T(reg) cells resulted in modulation of their ratio that closely paralleled disease course. Our data show that rapamycin inhibits RR-EAE, provide evidence for the immunological mechanisms, and indicate this compound as a potential candidate for the treatment of multiple sclerosis.

KW - Animals

KW - Antigens, Differentiation, T-Lymphocyte

KW - Antigens, Surface

KW - Disease Models, Animal

KW - Drug Administration Routes

KW - Encephalomyelitis, Autoimmune, Experimental

KW - Female

KW - Immune Tolerance

KW - Immunosuppressive Agents

KW - Interferon-gamma

KW - Interleukin-17

KW - Mice

KW - Multiple Sclerosis, Relapsing-Remitting

KW - Myelin Proteolipid Protein

KW - Peptide Fragments

KW - Phenotype

KW - Secondary Prevention

KW - Sirolimus

KW - T-Lymphocytes, Regulatory

KW - Treatment Outcome

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jneuroim.2010.01.001

DO - 10.1016/j.jneuroim.2010.01.001

M3 - SCORING: Journal article

C2 - 20149931

VL - 220

SP - 52

EP - 63

JO - J NEUROIMMUNOL

JF - J NEUROIMMUNOL

SN - 0165-5728

IS - 1-2

ER -