TY - JOUR
T1 - Successful modulation of murine lupus nephritis with tuftsin-phosphorylcholine
AU - Bashi, Tomer
AU - Blank, Miri
AU - Ben-Ami Shor, Dana
AU - Fridkin, Mati
AU - Versini, Mathilde
AU - Gendelman, Omer
AU - Volkov, Alexander
AU - Barshak, Iris
AU - Shoenfeld, Yehuda
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - In areas where helminths infections are common, autoimmune diseases are rare. Treatment with helminths and ova from helminths, improved clinical findings of inflammatory bowel disease, multiple-sclerosis and rheumatoid-arthritis. The immunomodulatory functions of some helminths were attributed to the phosphorylcholine (PC) moiety. We aimed to decipher the tolerogenic potential of Tuftsin-PC (TPC) compound in mice genetically prone to develop lupus.Lupus prone NZBXW/F1 mice received subcutaneously TPC (5μg/1ml), 3 times a week starting at 14 weeks age. Autoantibodies were tested by ELISA, T-regulatory-cells by FACS, cytokines profile by RT-PCR and cytokines protein levels by DuoSet ELISA. Glomerulonephritis was addressed by detection of proteinuria, and immunoglobulin complex deposition in the mesangium of the kidneys of the mice by immunofluorescence. Our results show that TPC attenuated the development of glomerulonephritis in lupus prone mice, in particular, it ameliorated proteinuria (p<0.02), and reduced immunoglobulin deposition in the kidney mesangium. TPC also enhanced the expression of TGFβ and IL-10 (p<0.001), and inhibited the production of IFNγ and IL-17 (p<0.03). TPC Significantly enhanced the expansion of CD4+CD25+FOXP3+ T-regulatory cells (Tregs) phenotype in the treated mice.These data indicate that TPC hampered lupus development in genetically lupus prone mice which was exemplified by moderate glomerulonephritis, attenuation of pro-inflammatory cytokines and enhancement of anti-inflammatory cytokines expression, as well as Tregs expansion. Our results propose harnessing novel natural therapy for lupus patients.
AB - In areas where helminths infections are common, autoimmune diseases are rare. Treatment with helminths and ova from helminths, improved clinical findings of inflammatory bowel disease, multiple-sclerosis and rheumatoid-arthritis. The immunomodulatory functions of some helminths were attributed to the phosphorylcholine (PC) moiety. We aimed to decipher the tolerogenic potential of Tuftsin-PC (TPC) compound in mice genetically prone to develop lupus.Lupus prone NZBXW/F1 mice received subcutaneously TPC (5μg/1ml), 3 times a week starting at 14 weeks age. Autoantibodies were tested by ELISA, T-regulatory-cells by FACS, cytokines profile by RT-PCR and cytokines protein levels by DuoSet ELISA. Glomerulonephritis was addressed by detection of proteinuria, and immunoglobulin complex deposition in the mesangium of the kidneys of the mice by immunofluorescence. Our results show that TPC attenuated the development of glomerulonephritis in lupus prone mice, in particular, it ameliorated proteinuria (p<0.02), and reduced immunoglobulin deposition in the kidney mesangium. TPC also enhanced the expression of TGFβ and IL-10 (p<0.001), and inhibited the production of IFNγ and IL-17 (p<0.03). TPC Significantly enhanced the expansion of CD4+CD25+FOXP3+ T-regulatory cells (Tregs) phenotype in the treated mice.These data indicate that TPC hampered lupus development in genetically lupus prone mice which was exemplified by moderate glomerulonephritis, attenuation of pro-inflammatory cytokines and enhancement of anti-inflammatory cytokines expression, as well as Tregs expansion. Our results propose harnessing novel natural therapy for lupus patients.
KW - Autoimmunity
KW - Helminths
KW - Lupus mice
KW - Phosphorylcholine
KW - Tuftsin
UR - http://www.scopus.com/inward/record.url?scp=84928581414&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2015.03.001
DO - 10.1016/j.jaut.2015.03.001
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AN - SCOPUS:84928581414
SN - 0896-8411
VL - 59
SP - 1
EP - 7
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
ER -