Plasmacytoid predendritic cells initiate psoriasis through interferon-α production

Journal of Experimental Medicine - Tập 202 Số 1 - Trang 135-143 - 2005
Frank O. Nestle1, Curdin Conrad1, Adrian Tun-Kyi1, Bernhard Homey2, Michael Gombert2, Onur Boyman1, Günter Burg1, Yong-Jun Liu3, Michel Gilliet1
11Department of Dermatology, University Hospital of Zurich, 8091 Zurich, Switzerland
22Department of Dermatology, Heinrich-Heine-University, 40225 Düsseldorf, Germany
33Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030

Tóm tắt

Psoriasis is one of the most common T cell–mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-α–producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-α early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-α signaling or inhibiting the ability of PDCs to produce IFN-α prevented the T cell–dependent development of psoriasis. Furthermore, IFN-α reconstitution experiments demonstrated that PDC-derived IFN-α is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-α represent potential early targets for the treatment of psoriasis.

Từ khóa


Tài liệu tham khảo

2003, Lancet., 361, 1197, 10.1016/S0140-6736(03)12954-6

2004, Trends Immunol., 25, 295, 10.1016/j.it.2004.03.006

1997, Immunol. Today., 18, 209, 10.1016/S0167-5699(97)01031-1

2001, N. Engl. J. Med., 345, 340, 10.1056/NEJM200108023450506

1996, J. R. Soc. Med., 89, 315, 10.1177/014107689608900604

2004, J. Clin. Invest., 113, 1664, 10.1172/JCI200422147

2004, Dermatol. Clin., 22, 349, 10.1016/j.det.2004.03.010

2005, Annu. Rev. Immunol., 23, 275, 10.1146/annurev.immunol.23.021704.115633

1999, Science., 284, 1835, 10.1126/science.284.5421.1835

1999, Nat. Med., 5, 919, 10.1038/11360

2000, J. Exp. Med., 192, 219, 10.1084/jem.192.2.219

2003, Blood., 101, 3520, 10.1182/blood-2002-10-3063

2001, Science., 294, 1540, 10.1126/science.1064890

2003, J. Exp. Med., 198, 823, 10.1084/jem.20020437

2001, Am. J. Pathol., 159, 237, 10.1016/S0002-9440(10)61689-6

2000, J. Immunol., 165, 4062, 10.4049/jimmunol.165.7.4062

2002, J. Invest. Dermatol., 119, 1096, 10.1046/j.1523-1747.2002.19515.x

2003, J. Invest. Dermatol., 121, 1409, 10.1111/j.1523-1747.2003.12623.x

2004, Arch. Dermatol., 140, 1490

2004, J. Invest. Dermatol., 122, 51, 10.1046/j.0022-202X.2003.22113.x

1994, J. Interferon Res., 14, 229, 10.1089/jir.1994.14.229

1995, J. Histochem. Cytochem., 43, 47, 10.1177/43.1.7822763

2004, J. Invest. Dermatol., 122, 717, 10.1111/j.0022-202X.2004.22322.x

2000, Immunity., 13, 643, 10.1016/S1074-7613(00)00064-9

1991, Br. J. Dermatol., 125, 463, 10.1111/j.1365-2133.1991.tb14774.x

1993, Acta Derm. Venereol., 73, 395, 10.2340/0001555573395

2000, Clin. Exp. Dermatol., 25, 351

2005, Eur. J. Dermatol., 15, 107

2001, J. Exp. Med., 194, 1823, 10.1084/jem.194.12.1823

1997, J. Exp. Med., 185, 1101, 10.1084/jem.185.6.1101

1998, J. Autoimmun., 11, 465, 10.1006/jaut.1998.0215

2000, Immunity., 13, 539, 10.1016/S1074-7613(00)00053-4

2004, Nat. Immunol., 5, 1061, 10.1038/ni1118

1993, J. Immunol., 150, 1715, 10.4049/jimmunol.150.5.1715

1994, J. Infect. Dis., 169, 807, 10.1093/infdis/169.4.807

2004, J. Exp. Med., 199, 731, 10.1084/jem.20031482

2004, Br. J. Dermatol., 150, 852, 10.1111/j.1365-2133.2004.05863.x

1993, J. Biol. Chem., 268, 10895, 10.1016/S0021-9258(18)82069-5

2001, J. Exp. Med., 194, 863, 10.1084/jem.194.6.863

2001, Eur. J. Immunol., 31, 3388, 10.1002/1521-4141(200111)31:11<3388::AID-IMMU3388>3.0.CO;2-Q

2004, Rheumatology (Oxford)., 43, 453, 10.1093/rheumatology/keh115

2004, Nat. Rev. Immunol., 4, 211, 10.1038/nri1310

2004, Science., 303, 1529, 10.1126/science.1093616

2005, Nat. Med., 11, 138, 10.1038/nm1176

2004, Immunity., 20, 539, 10.1016/S1074-7613(04)00108-6

1994, J. Clin. Invest., 94, 202, 10.1172/JCI117308

2003, Nat. Immunol., 4, 1009, 10.1038/ni978

1998, Immunity., 8, 591, 10.1016/S1074-7613(00)80564-6

2003, J. Interferon Cytokine Res., 23, 513, 10.1089/10799900360708632

2003, N. Engl. J. Med., 349, 2014, 10.1056/NEJMoa030409

2001, Lancet., 357, 1842, 10.1016/S0140-6736(00)04954-0

2004, Exp. Dermatol., 13, 193, 10.1111/j.0906-6705.2004.00205.x

2005, Nature., 434, 1035, 10.1038/nature03547

2005, Annu. Rev. Immunol., 23, 307, 10.1146/annurev.immunol.23.021704.115843

2003, Autoimmunity., 36, 511, 10.1080/08916930310001605873

1994, Lancet., 343, 1167, 10.1016/S0140-6736(94)90276-3

2001, Clin. Rheumatol., 20, 297, 10.1007/PL00011206

2000, Lupus., 9, 664, 10.1191/096120300674499064

2003, J. Exp. Med., 197, 711, 10.1084/jem.20021553

1999, J. Immunol., 163, 6306, 10.4049/jimmunol.163.11.6306

1995, Diabetes., 44, 658, 10.2337/diab.44.6.658

1993, Science., 260, 1942, 10.1126/science.8100367

2004, J. Immunol., 173, 2815, 10.4049/jimmunol.173.4.2815

Thông tin
Thông tin xuất bản

Journal of Experimental Medicine

Tập 202 Số 1

135-143

Thông tin tác giả