TY - JOUR
T1 - Dickkopf proteins in pathological inflammatory diseases
AU - Park, Min Hee
AU - Shin, Jae Hun
AU - Bothwell, Alfred L.M.
AU - Chae, Wook Jin
N1 - Funding Information:
This work was supported by Massey Cancer Center Research Funds (W.‐J. C.), the Harrison Scholar Funds (W.‐J. C.), the Massey Cancer Center leadership award (W.‐J. C.), Institutional Research Grant 18‐159‐43 from the American Cancer Society(W.‐J. C.), and NIH R01 CA168670 (A.L.M.B)
Publisher Copyright:
©2021 Society for Leukocyte Biology.
PY - 2022/4
Y1 - 2022/4
N2 - The human body encounters various challenges. Tissue repair and regeneration processes are augmented after tissue injury to reinstate tissue homeostasis. The Wnt pathway plays a crucial role in tissue repair since it induces target genes required for cell proliferation and differentiation. Since tissue injury causes inflammatory immune responses, it has become increasingly clear that the Wnt ligands can function as immunomodulators while critical for tissue homeostasis. The Wnt pathway and Wnt ligands have been studied extensively in cancer biology and developmental biology. While the Wnt ligands are being studied actively, how the Wnt antagonists and their regulatory mechanisms can modulate immune responses during chronic pathological inflammation remain elusive. This review summarizes DKK family proteins as immunomodulators, aiming to provide an overarching picture for tissue injury and repair. To this end, we first review the Wnt pathway components and DKK family proteins. Next, we will review DKK family proteins (DKK1, 2, and 3) as a new class of immunomodulatory protein in cancer and other chronic inflammatory diseases. Taken together, DKK family proteins and their immunomodulatory functions in chronic inflammatory disorders provide novel insights to understand immune diseases and make them attractive molecular targets for therapeutic intervention.
AB - The human body encounters various challenges. Tissue repair and regeneration processes are augmented after tissue injury to reinstate tissue homeostasis. The Wnt pathway plays a crucial role in tissue repair since it induces target genes required for cell proliferation and differentiation. Since tissue injury causes inflammatory immune responses, it has become increasingly clear that the Wnt ligands can function as immunomodulators while critical for tissue homeostasis. The Wnt pathway and Wnt ligands have been studied extensively in cancer biology and developmental biology. While the Wnt ligands are being studied actively, how the Wnt antagonists and their regulatory mechanisms can modulate immune responses during chronic pathological inflammation remain elusive. This review summarizes DKK family proteins as immunomodulators, aiming to provide an overarching picture for tissue injury and repair. To this end, we first review the Wnt pathway components and DKK family proteins. Next, we will review DKK family proteins (DKK1, 2, and 3) as a new class of immunomodulatory protein in cancer and other chronic inflammatory diseases. Taken together, DKK family proteins and their immunomodulatory functions in chronic inflammatory disorders provide novel insights to understand immune diseases and make them attractive molecular targets for therapeutic intervention.
KW - Wnt
KW - antagonist
KW - cancer
KW - immunology
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U2 - 10.1002/JLB.3RI0721-385R
DO - 10.1002/JLB.3RI0721-385R
M3 - Review article
C2 - 34890067
AN - SCOPUS:85121362377
SN - 0741-5400
VL - 111
SP - 893
EP - 901
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 4
ER -