title: Regulatory B cells suppress imiquimod-induced, psoriasis-like skin inflammation.
abstract: Psoriasis is an inflammatory cutaneous disorder characterized by marked epidermal thickening and Th1 and Th17 cell infiltration. At present, the contribution of B cells to the pathogenesis of psoriasis is unclear. In mice, topical application of imiquimod induces inflamed skin lesions and serves as an experimental animal model for human psoriasis. In this study, we showed that imiquimod-induced skin inflammation was more severe in CD19(-/-) than WT mice. These inflammatory responses were negatively regulated by a unique IL-10-producing CD1d(hi)CD5(+) regulatory B cell subset (B10 cells) that was absent in CD19(-/-) mice and represented only 1-2% of splenic B220(+) cells in WT mice. Splenic B10 cells entered the circulation and migrated to draining LNs during imiquimod-induced skin inflammation, thereby suppressing IFN-γ and IL-17 production. Furthermore, adoptive transfer of these B10 cells from WT mice reduced inflammation in CD19(-/-) mice. The present findings provide direct evidence that B10 cells regulate imiquimod-induced skin inflammation and offer insights into regulatory B cell-based therapies for the treatment of psoriasis.
authors: 1.Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. yanaba@jikei.ac.jp.
authors: Koichi
authors: K
authors: Yanaba
authors: Masahiro
authors: M
authors: Kamata
authors: Nobuko
authors: N
authors: Ishiura
authors: Sayaka
authors: S
authors: Shibata
authors: Yoshihide
authors: Y
authors: Asano
authors: Yayoi
authors: Y
authors: Tada
authors: Makoto
authors: M
authors: Sugaya
authors: Takafumi
authors: T
authors: Kadono
authors: Thomas F
authors: TF
authors: Tedder
authors: Shinichi
authors: S
authors: Sato
mesh_terms: D000634:Aminoquinolines / Q000009:adverse effects*; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D055610:Antigens, CD1d / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D006801:Humans; D000077271:Imiquimod; D007249:Inflammation / Q000097:blood / Q000139:chemically induced* / Q000150:complications / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011565:Psoriasis / Q000097:blood / Q000139:chemically induced* / Q000150:complications / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000473:pathology*; D013154:Spleen / Q000473:pathology
chemical_list: D000634:Aminoquinolines; D018941:Antigens, CD19; D055610:Antigens, CD1d; D018956:CD5 Antigens; D020381:Interleukin-17; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma; D000077271:Imiquimod
keywords: B10 cells; IL-10; cytokines
references: J Exp Med. 2003 Apr 7;197(7):875-83
references: 12668647
references: N Engl J Med. 2009 Jul 30;361(5):496-509
references: 19641206
references: Eur J Immunol. 2010 Oct;40(10):2686-91
references: 20809522
references: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20878-83
references: 18093919
references: Ann Rheum Dis. 2008 Nov;67(11):1647-8
references: 18854517
references: Immunity. 2010 Jan 29;32(1):129-40
references: 20079667
references: J Invest Dermatol. 1998 Dec;111(6):1235-6
references: 9856850
references: J Clin Invest. 1998 Feb 15;101(4):783-94
references: 9466973
references: Nat Immunol. 2001 Feb;2(2):91
references: 11175798
references: J Immunol. 1995 Oct 15;155(8):3734-41
references: 7561077
references: J Am Acad Dermatol. 2004 May;50(5):657-75; quiz 676-8
references: 15097948
references: Immunol Rev. 2008 Jun;223:284-99
references: 18613843
references: Am J Pathol. 2011 Feb;178(2):735-43
references: 21281806
references: Br J Dermatol. 2007 Dec;157 Suppl 2:8-13
references: 18067624
references: J Immunol. 2007 Jul 15;179(2):1369-80
references: 17617630
references: J Immunol. 2010 Aug 15;185(4):2240-52
references: 20624940
references: J Clin Invest. 2008 Oct;118(10):3420-30
references: 18802481
references: Arch Dermatol. 1999 Feb;135(2):187-92
references: 10052405
references: Immunol Rev. 2008 Aug;224:201-14
references: 18759928
references: Blood. 2011 Jan 13;117(2):530-41
references: 20962324
references: J Invest Dermatol. 2008 May;128(5):1207-11
references: 18200064
references: Gastroenterology. 1997 Aug;113(2):383-9
references: 9247454
references: J Immunol. 2011 Jul 1;187(1):181-9
references: 21606247
references: Nat Immunol. 2000 Dec;1(6):475-82
references: 11101868
references: J Immunol. 2008 Mar 1;180(5):2863-75
references: 18292508
references: Arthritis Rheum. 2007 Aug;56(8):2715-8
references: 17665440
references: J Immunol. 1996 Nov 15;157(10):4371-8
references: 8906812
references: J Immunol. 2009 Jun 15;182(12):7459-72
references: 19494269
references: Am J Pathol. 2006 Sep;169(3):954-66
references: 16936269
references: Ann Rheum Dis. 2008 Jul;67(7):1056-7
references: 18556453
references: Arch Dermatol. 2004 Dec;140(12):1490-5
references: 15611427
references: Arch Dermatol Res. 2008 Nov;300(10):551-9
references: 18797896
references: Pharmacol Rev. 2003 Jun;55(2):241-69
references: 12773629
references: Arch Dermatol. 2002 Oct;138(10):1341-6
references: 12374540
references: Br J Dermatol. 2011 Mar;164(3):670-2
references: 21062268
references: Immunity. 1995 Jul;3(1):39-50
references: 7542548
references: Clin Exp Dermatol. 2010 Aug;35(6):645-9
references: 19843085
references: J Immunol. 2009 May 1;182(9):5836-45
references: 19380832
references: Immunity. 2008 May;28(5):639-50
references: 18482568