IL-17 protects T cells from apoptosis and contributes to development of ALPS-like phenotypes

Elena Boggio, Nausicaa Clemente, Anna Mondino, Giuseppe Cappellano, Elisabetta Orilieri, Casimiro L. Gigliotti, Erika Toth, Ugo Ramenghi, Umberto Dianzani, Annalisa Chiocchetti

Research output: Contribution to journalArticle

Abstract

In autoimmune/lymphoproliferative syndrome (ALPS), defective Fas death receptor function causes lymphadenomegaly/splenomegaly, the expansion of T-cell receptor αβ+ CD4/CD8 double-negative T cells, and frequent development of hematologic autoimmunity. Dianzani autoimmune lymphoproliferative disease (DALD) has a similar phenotype but lacks the expansion of double-negative T cells. This work shows that patients with ALPS and DALD have high serum levels of interleukin 17A (IL-17A), IL-17F, and IL-17AF, which are involved in several autoimmune diseases, and that their T cells show increased secretion of these cytokines upon activation in vitro. The following data indicate that these cytokines may contribute to ALPS and DALD: (1) recombinant IL-17A and IL-17F significantly inhibit Fas-induced cell death in Fas-sensitive T cells from healthy donors; (2) this inhibitory effect is also induced by the patients' serum and is reversed by anti-IL-17A antibodies; (3) IL-17A neutralization substantially increases Fas-induced cell death in T cells from ALPS and DALD patients in vitro; and (4) treatment with anti-IL-17A antibodies ameliorates the autoimmune manifestations and, at a lesser extent, the lymphoproliferative phenotype and prolongs survival in MRLlpr/lpr mice, which are an animal model of ALPS. These data suggest that IL-17A and IL-17F could be targeted therapeutically to improve Fas function in ALPS and DALD.

Original languageEnglish
Pages (from-to)1178-1186
Number of pages9
JournalBlood
Volume123
Issue number8
DOIs
Publication statusPublished - Feb 20 2014

Fingerprint

Autoimmune Lymphoproliferative Syndrome
T-cells
Interleukin-17
Apoptosis
T-Lymphocytes
Phenotype
Cell death
Cell Death
Cytokines
CD95 Antigens
Death Domain Receptors
Antibodies
Splenomegaly
T-Cell Antigen Receptor
Serum
Autoimmunity
Autoimmune Diseases
Animals
Animal Models
Chemical activation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Boggio, E., Clemente, N., Mondino, A., Cappellano, G., Orilieri, E., Gigliotti, C. L., ... Chiocchetti, A. (2014). IL-17 protects T cells from apoptosis and contributes to development of ALPS-like phenotypes. Blood, 123(8), 1178-1186. https://doi.org/10.1182/blood-2013-07-518167

IL-17 protects T cells from apoptosis and contributes to development of ALPS-like phenotypes. / Boggio, Elena; Clemente, Nausicaa; Mondino, Anna; Cappellano, Giuseppe; Orilieri, Elisabetta; Gigliotti, Casimiro L.; Toth, Erika; Ramenghi, Ugo; Dianzani, Umberto; Chiocchetti, Annalisa.

In: Blood, Vol. 123, No. 8, 20.02.2014, p. 1178-1186.

Research output: Contribution to journalArticle

Boggio, E, Clemente, N, Mondino, A, Cappellano, G, Orilieri, E, Gigliotti, CL, Toth, E, Ramenghi, U, Dianzani, U & Chiocchetti, A 2014, 'IL-17 protects T cells from apoptosis and contributes to development of ALPS-like phenotypes', Blood, vol. 123, no. 8, pp. 1178-1186. https://doi.org/10.1182/blood-2013-07-518167
Boggio E, Clemente N, Mondino A, Cappellano G, Orilieri E, Gigliotti CL et al. IL-17 protects T cells from apoptosis and contributes to development of ALPS-like phenotypes. Blood. 2014 Feb 20;123(8):1178-1186. https://doi.org/10.1182/blood-2013-07-518167
Boggio, Elena ; Clemente, Nausicaa ; Mondino, Anna ; Cappellano, Giuseppe ; Orilieri, Elisabetta ; Gigliotti, Casimiro L. ; Toth, Erika ; Ramenghi, Ugo ; Dianzani, Umberto ; Chiocchetti, Annalisa. / IL-17 protects T cells from apoptosis and contributes to development of ALPS-like phenotypes. In: Blood. 2014 ; Vol. 123, No. 8. pp. 1178-1186.
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AU - Gigliotti, Casimiro L.

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