The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation

被引：132

作者：

Chae, Wook-Jin ^{[1
]}

Ehrlich, Allison K. ^{[2
]}

Chan, Pamela Y. ^{[1
]}

Teixeira, Alexandra M. ^{[3
]}

Henegariu, Octavian ^{[4
]}

Hao, Liming ^{[3
]}

Shin, Jae Hun ^{[1
]}

Park, Jong-Hyun ^{[1
]}

Tang, Wai Ho ^{[5
,6
]}

Kim, Sang-Taek ^{[7
]}

Maher, Stephen E. ^{[1
]}

Goldsmith-Pestana, Karen ^{[2
]}

Shan, Peiying ^{[8
]}

Hwa, John ^{[5
,6
]}

Lee, Patty J. ^{[8
]}

Krause, Diane S. ^{[3
,9
,10
]}

Rothlin, Carla V. ^{[1
]}

McMahon-Pratt, Diane ^{[2
]}

Bothwell, Alfred L. M. ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Yale Sch Publ Hlth, Dept Epidemiol Microbial Dis, 333 Cedar St, New Haven, CT 06520 USA

[3] Yale Univ, Sch Med, Dept Pathol, 333 Cedar St, New Haven, CT 06520 USA

[4] Yale Univ, Sch Med, Dept Neurosurg, 333 Cedar St, New Haven, CT 06520 USA

[5] Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA

[6] Yale Univ, Sch Med, Cardiovasc Res Ctr, 333 Cedar St, New Haven, CT 06520 USA

[7] Yale Univ, Sch Med, Dept Rheumatol, 333 Cedar St, New Haven, CT 06520 USA

[8] Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, 333 Cedar St, New Haven, CT 06520 USA

[9] Yale Univ, Sch Med, Dept Lab Med, 333 Cedar St, New Haven, CT 06520 USA

[10] Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06520 USA

来源：

IMMUNITY | 2016年 / 44卷 / 02期

关键词：

LEISHMANIA-MAJOR; MURINE MODEL; C-MAF; PLATELETS; INFECTION; IMMUNE; DIFFERENTIATION; EXPRESSION; PROTEIN; INTERLEUKIN-4;

D O I：

10.1016/j.immuni.2016.01.008

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Exposure to a plethora of environmental challenges commonly triggers pathological type 2 cell-mediated inflammation. Here we report the pathological role of the Wnt antagonist Dickkopf-1 (Dkk-1) upon allergen challenge or non-healing parasitic infection. The increased circulating amounts of Dkk-1 polarized T cells to T helper 2 (Th2) cells, stimulating a marked simultaneous induction of the transcription factors c-Maf and Gata-3, mediated by the kinases p38 MAPK and SGK-1, resulting in Th2 cell cytokine production. Circulating Dkk-1 was primarily from platelets, and the increase of Dkk-1 resulted in formation of leukocyte-platelet aggregates (LPA) that facilitated leukocyte infiltration to the affected tissue. Functional inhibition of Dkk-1 impaired Th2 cell cytokine production and leukocyte infiltration, protecting mice from house dust mite (HDM)-induced asthma or Leishmania major infection. These results highlight that Dkk-1 from thrombocytes is an important regulator of leukocyte infiltration and polarization of immune responses in pathological type 2 cell-mediated inflammation.

引用

页码：246 / 258

页数：13

共 63 条

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