TY - JOUR
T1 - The Wnt Antagonist Dickkopf-Promotes Pathological Type 2 Cell-Mediated Inflammation
AU - Chae, Wook Jin
AU - Ehrlich, Allison K.
AU - Chan, Pamela Y.
AU - Teixeira, Alexandra M.
AU - Henegariu, Octavian
AU - Hao, Liming
AU - Shin, Jae Hun
AU - Park, Jong Hyun
AU - Tang, Wai Ho
AU - Kim, Sang Taek
AU - Maher, Stephen E.
AU - Goldsmith-Pestana, Karen
AU - Shan, Peiying
AU - Hwa, John
AU - Lee, Patty J.
AU - Krause, Diane S.
AU - Rothlin, Carla V.
AU - McMahon-Pratt, Diane
AU - Bothwell, Alfred L.M.
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/2/16
Y1 - 2016/2/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84958103896&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958103896&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2016.01.008
DO - 10.1016/j.immuni.2016.01.008
M3 - Article
C2 - 26872695
AN - SCOPUS:84958103896
SN - 1074-7613
VL - 44
SP - 246
EP - 258
JO - Immunity
JF - Immunity
IS - 2
ER -
