@article{1d34d141bdf549eda88a92fccd0b783e,
title = "The Wnt Antagonist Dickkopf-Promotes Pathological Type 2 Cell-Mediated Inflammation",
abstract = "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-(Dkk-1) upon allergen challenge or non-healing parasitic infection. The increased circulating amounts of Dkk-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-was primarily from platelets, and the increase of Dkk-resulted in formation of leukocyte-platelet aggregates (LPA) that facilitated leukocyte infiltration to the affected tissue. Functional inhibition of Dkk-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-from thrombocytes is an important regulator of leukocyte infiltration and polarization of immune responses in pathological type 2 cell-mediated inflammation.",
author = "Chae, {Wook Jin} and Ehrlich, {Allison K.} and Chan, {Pamela Y.} and Teixeira, {Alexandra M.} and Octavian Henegariu and Liming Hao and Shin, {Jae Hun} and Park, {Jong Hyun} and Tang, {Wai Ho} and Kim, {Sang Taek} and Maher, {Stephen E.} and Karen Goldsmith-Pestana and Peiying Shan and John Hwa and Lee, {Patty J.} and Krause, {Diane S.} and Rothlin, {Carla V.} and Diane McMahon-Pratt and Bothwell, {Alfred L.M.}",
note = "Funding Information: We thank Gouzel Tokmulina and Tom Taylor for cell sorting and Christine Cote for technical help in AMNIS operation. This work was supported by NIH 1R21AI107957-01 and NIH 1R01CA168670-01 (both awarded to A.L.M.B.), AI093775 (D.M.-P.), R01 AI089824 (C.V.R.), and T32 AI007019 (P.Y.C.). AMNIS work was supported by the Shared Instrument Grant (1-S10-RR-026526-01). Funding Information: We thank Gouzel Tokmulina and Tom Taylor for cell sorting and Christine Cote for technical help in AMNIS operation. This work was supported by NIH 1R21AI107957-01 and NIH 1R01CA168670-01 (both awarded to A.L.M.B.), AI093775 (D.M.-P.), R01 AI089824 (C.V.R.), and T32 AI007019 (P.Y.C.). AMNIS work was supported by the Shared Instrument Grant (1-S10-RR-026526-01). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = feb,
day = "16",
doi = "10.1016/j.immuni.2016.01.008",
language = "English (US)",
volume = "44",
pages = "246--258",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",
}