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Leptin is secreted by adipocytes, the placenta, and the stomach. It not only controls appetite through leptin receptors in the hypothalamus, it also regulates immunity. In the current study, we produced leptin-deficient MRL/Mp-Fas(lpr) mice to investigate the potential role of leptin in autoimmunity. C57BL/6J-ob/ob mice were backcrossed with MRL/Mp-Fas(lpr) mice, which develop human systemic lupus erythematosus (SLE)-like lesions. The effects of leptin deficiency on various SLE-like manifestations were investigated in MRL/Mp-Fas(lpr) mice. The regulatory T cell population in the spleen was analyzed by flow cytometry, and the effects of leptin on regulatory T cells and Th17 cells were evaluated in vitro. Compared with leptin-producing MRL/Mp-Fas(lpr) mice, leptin-deficient MRL/Mp-Fas(lpr) mice showed less marked splenomegaly and a particularly low population of CD3(+)CD4(-)CD8(-)B220(+) T cells (lpr cells). Their serum concentrations of Abs to dsDNA were lower, and renal histological changes at age 20 wk were ameliorated. Regulatory T cells were increased in the spleens of leptin-deficient MRL/Mp-Fas(lpr) mice. Leptin suppressed regulatory T cells and enhanced Th17 cells in vitro. In conclusion, blockade of leptin signaling may be of therapeutic benefit in patients with SLE and other autoimmune diseases.

Titel:	Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice.
Autor/in / Beteiligte Person:	Fujita, Y ; Fujii, T ; Mimori, T ; Sato, T ; Nakamura, T ; Iwao, H ; Nakajima, A ; Miki, M ; Sakai, T ; Kawanami, T ; Tanaka, M ; Masaki, Y ; Fukushima, T ; Okazaki, T ; Umehara, H
Zeitschrift:	Journal of immunology (Baltimore, Md. : 1950), Jg. 192 (2014-02-01), Heft 3, S. 979
Veröffentlichung:	Bethesda, MD : American Association of Immunologists ; <i>Original Publication</i>: Baltimore : Williams & Wilkins, c1950-, 2014
Medientyp:	academicJournal
ISSN:	1550-6606 (electronic)
DOI:	10.4049/jimmunol.1301685
Schlagwort:	Animals Antibodies, Antinuclear biosynthesis Antibodies, Antinuclear blood Autoantigens immunology Cells, Cultured Crosses, Genetic DNA immunology Female Immunoglobulin G blood Kidney pathology Kidney physiopathology Leptin immunology Lupus Erythematosus, Systemic immunology Lupus Erythematosus, Systemic pathology Lymphocyte Count Male Mice, Inbred C57BL Mice, Inbred MRL lpr Mice, Obese Rheumatoid Factor blood Signal Transduction immunology Specific Pathogen-Free Organisms Spleen immunology Spleen pathology Splenomegaly etiology Splenomegaly immunology Splenomegaly pathology T-Lymphocyte Subsets pathology T-Lymphocytes, Regulatory pathology Th17 Cells immunology Th17 Cells pathology Leptin deficiency Lupus Erythematosus, Systemic prevention & control T-Lymphocyte Subsets immunology T-Lymphocytes, Regulatory immunology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [J Immunol] 2014 Feb 01; Vol. 192 (3), pp. 979-84. <i>Date of Electronic Publication: </i>2014 Jan 03. MeSH Terms: Leptin / deficiency ; Lupus Erythematosus, Systemic / prevention & control ; T-Lymphocyte Subsets / immunology ; T-Lymphocytes, Regulatory / immunology ; Animals ; Antibodies, Antinuclear / biosynthesis ; Antibodies, Antinuclear / blood ; Autoantigens / immunology ; Cells, Cultured ; Crosses, Genetic ; DNA / immunology ; Female ; Immunoglobulin G / blood ; Kidney / pathology ; Kidney / physiopathology ; Leptin / immunology ; Lupus Erythematosus, Systemic / immunology ; Lupus Erythematosus, Systemic / pathology ; Lymphocyte Count ; Male ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Mice, Obese ; Rheumatoid Factor / blood ; Signal Transduction / immunology ; Specific Pathogen-Free Organisms ; Spleen / immunology ; Spleen / pathology ; Splenomegaly / etiology ; Splenomegaly / immunology ; Splenomegaly / pathology ; T-Lymphocyte Subsets / pathology ; T-Lymphocytes, Regulatory / pathology ; Th17 Cells / immunology ; Th17 Cells / pathology References: Am J Clin Nutr. 1997 Aug;66(2):460S-463S. (PMID: 9250133) ; Biochem Biophys Res Commun. 2002 Nov 1;298(3):297-302. (PMID: 12413939) ; J Am Soc Nephrol. 2001 Dec;12(12):2652-2663. (PMID: 11729234) ; Endocrinology. 1997 Mar;138(3):947-54. (PMID: 9048594) ; Nature. 1992 May 7;357(6373):77-80. (PMID: 1574128) ; J Immunol. 2012 Mar 1;188(5):2070-3. (PMID: 22291185) ; Arthritis Rheum. 2012 Nov;64(11):3564-73. (PMID: 22833425) ; Immunity. 2007 Feb;26(2):241-55. (PMID: 17307705) ; Nature. 1994 Dec 1;372(6505):425-32. (PMID: 7984236) ; Diabetologia. 1978 Mar;14(3):141-8. (PMID: 350680) ; Metabolism. 1999 Jun;48(6):745-8. (PMID: 10381149) ; Curr Biol. 1996 Sep 1;6(9):1170-80. (PMID: 8805376) ; Br J Dermatol. 2002 Aug;147(2):331-6. (PMID: 12174107) ; Am J Clin Nutr. 1980 Jan;33(1):13-6. (PMID: 6965559) ; Eur J Pharmacol. 1999 Jan 22;365(2-3):273-9. (PMID: 9988112) ; Rheumatol Int. 2002 Aug;22(4):138-41. (PMID: 12172951) ; Clin Immunol. 2008 Jun;127(3):385-93. (PMID: 18373953) ; Nature. 1995 Oct 12;377(6549):530-2. (PMID: 7566151) ; Lab Anim Sci. 1998 Feb;48(1):103-4. (PMID: 9517901) ; J Immunol. 2001 Oct 15;167(8):4593-9. (PMID: 11591788) ; J Clin Immunol. 2010 Mar;30(2):221-5. (PMID: 20107878) ; Nat Med. 1996 Jul;2(7):800-3. (PMID: 8673927) ; J Biol Chem. 1996 Jun 14;271(24):13939-42. (PMID: 8663251) ; Clin Exp Immunol. 2002 Apr;128(1):21-6. (PMID: 11982586) ; Biochem Biophys Res Commun. 1998 May 29;246(3):752-9. (PMID: 9618284) ; Arthritis Res Ther. 2010;12(2):R53. (PMID: 20334681) ; J Immunol. 1978 Apr;120(4):1375-7. (PMID: 347001) ; J Immunol. 1996 Jul 1;157(1):417-26. (PMID: 8683147) ; J Immunol. 2009 Sep 1;183(5):3160-9. (PMID: 19657089) ; Biochem Biophys Res Commun. 1997 Mar 17;232(2):383-7. (PMID: 9125186) ; J Autoimmun. 2009 Sep;33(2):125-34. (PMID: 19596182) ; Nat Med. 1996 May;2(5):585-9. (PMID: 8616721) ; J Immunol. 1983 Apr;130(4):1713-8. (PMID: 6187819) ; Blood. 1999 Mar 1;93(5):1668-76. (PMID: 10029596) ; Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2691-8. (PMID: 17690315) ; Clin Exp Immunol. 2002 Nov;130(2):224-32. (PMID: 12390309) ; Diabetes. 1999 Sep;48(9):1822-9. (PMID: 10480614) ; Nature. 1998 Aug 27;394(6696):897-901. (PMID: 9732873) ; J Immunol. 2008 Dec 15;181(12):8761-6. (PMID: 19050297) ; Endocrinology. 1997 Aug;138(8):3395-401. (PMID: 9231793) ; Clin Exp Immunol. 2013 Jan;171(1):63-8. (PMID: 23199324) Substance Nomenclature: 0 (Antibodies, Antinuclear) ; 0 (Autoantigens) ; 0 (Immunoglobulin G) ; 0 (Leptin) ; 9007-49-2 (DNA) ; 9009-79-4 (Rheumatoid Factor) Entry Date(s): Date Created: 20140107 Date Completed: 20140325 Latest Revision: 20211021 Update Code: 20231215 PubMed Central ID: PMC3897175

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Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice.