Immunoregulatory role ofJα281 T cells in aged mice developing lupus-like nephritis

Guido Sireci, Domenica Russo, Francesco Dieli, Steven A. Porcelli, Masaru Taniguchi, Marco Pio La Manna, Diana Di Liberto, Francesco Scarpa, Alfredo Salerno

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Vα14Jα281 chains paired with some Vβ domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jα281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jα281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jα281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jα281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jα281+ cells, probably associated with the activation of marginal zone B cells.

Original languageEnglish (US)
Pages (from-to)425-433
Number of pages9
JournalEuropean Journal of Immunology
Volume37
Issue number2
DOIs
StatePublished - Feb 2007

Fingerprint

Lupus Nephritis
Knockout Mice
T-Lymphocytes
Natural Killer T-Cells
B-Lymphocytes
Immunoglobulin G
Systemic Lupus Erythematosus
Cardiolipins
Proteinuria
Autoantibodies
Autoimmune Diseases
Spleen
Antibodies

Keywords

  • Autoimmunity
  • Knockout
  • NKT cells

ASJC Scopus subject areas

  • Immunology

Cite this

Immunoregulatory role ofJα281 T cells in aged mice developing lupus-like nephritis. / Sireci, Guido; Russo, Domenica; Dieli, Francesco; Porcelli, Steven A.; Taniguchi, Masaru; La Manna, Marco Pio; Di Liberto, Diana; Scarpa, Francesco; Salerno, Alfredo.

In: European Journal of Immunology, Vol. 37, No. 2, 02.2007, p. 425-433.

Research output: Contribution to journalArticle

Sireci, G, Russo, D, Dieli, F, Porcelli, SA, Taniguchi, M, La Manna, MP, Di Liberto, D, Scarpa, F & Salerno, A 2007, 'Immunoregulatory role ofJα281 T cells in aged mice developing lupus-like nephritis', European Journal of Immunology, vol. 37, no. 2, pp. 425-433. https://doi.org/10.1002/eji.200636695
Sireci, Guido ; Russo, Domenica ; Dieli, Francesco ; Porcelli, Steven A. ; Taniguchi, Masaru ; La Manna, Marco Pio ; Di Liberto, Diana ; Scarpa, Francesco ; Salerno, Alfredo. / Immunoregulatory role ofJα281 T cells in aged mice developing lupus-like nephritis. In: European Journal of Immunology. 2007 ; Vol. 37, No. 2. pp. 425-433.
@article{df62fc7d28c2403796b58e070cb61af5,
title = "Immunoregulatory role ofJα281 T cells in aged mice developing lupus-like nephritis",
abstract = "Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Vα14Jα281 chains paired with some Vβ domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jα281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jα281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jα281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jα281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jα281+ cells, probably associated with the activation of marginal zone B cells.",
keywords = "Autoimmunity, Knockout, NKT cells",
author = "Guido Sireci and Domenica Russo and Francesco Dieli and Porcelli, {Steven A.} and Masaru Taniguchi and {La Manna}, {Marco Pio} and {Di Liberto}, Diana and Francesco Scarpa and Alfredo Salerno",
year = "2007",
month = "2",
doi = "10.1002/eji.200636695",
language = "English (US)",
volume = "37",
pages = "425--433",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "2",

}

TY - JOUR

T1 - Immunoregulatory role ofJα281 T cells in aged mice developing lupus-like nephritis

AU - Sireci, Guido

AU - Russo, Domenica

AU - Dieli, Francesco

AU - Porcelli, Steven A.

AU - Taniguchi, Masaru

AU - La Manna, Marco Pio

AU - Di Liberto, Diana

AU - Scarpa, Francesco

AU - Salerno, Alfredo

PY - 2007/2

Y1 - 2007/2

N2 - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Vα14Jα281 chains paired with some Vβ domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jα281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jα281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jα281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jα281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jα281+ cells, probably associated with the activation of marginal zone B cells.

AB - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Vα14Jα281 chains paired with some Vβ domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jα281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jα281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jα281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jα281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jα281+ cells, probably associated with the activation of marginal zone B cells.

KW - Autoimmunity

KW - Knockout

KW - NKT cells

UR - http://www.scopus.com/inward/record.url?scp=33947732677&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947732677&partnerID=8YFLogxK

U2 - 10.1002/eji.200636695

DO - 10.1002/eji.200636695

M3 - Article

C2 - 17273990

AN - SCOPUS:33947732677

VL - 37

SP - 425

EP - 433

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 2

ER -