TY - JOUR
T1 - Skin repair and immunoregulatory effects of myeloid suppressor cells from human cord blood in atopic dermatitis
AU - Kim, Chang Hyun
AU - Hong, Seung Min
AU - Kim, Sueon
AU - Yu, Jae Ik
AU - Jung, Soo Hyun
AU - Bang, Chul Hwan
AU - Lee, Ji Hyun
AU - Kim, Tai Gyu
N1 - Publisher Copyright:
Copyright © 2024 Kim, Hong, Kim, Yu, Jung, Bang, Lee and Kim.
PY - 2023
Y1 - 2023
N2 - Introduction: Previously, we achieved large-scale expansion of bone marrow-derived suppressor cells (MDSCs) derived from cluster of differentiation (CD)34+ cells cultured in human umbilical cord blood (hUCB) and demonstrated their immunomodulatory properties. In the present study, we assessed the therapeutic efficacy of hUCB-MDSCs in atopic dermatitis (AD). Methods: Dermatophagoides farinae (Df)-induced NC/Nga mice (clinical score of 7) were treated with hUCB-MDSCs or a control drug. The mechanisms underlying the therapeutic effects of hUCB-MDSCs were evaluated. Results and discussion: hUCB-MDSCs demonstrated immunosuppressive effects in both human and mouse CD4+ T cells. hUCB-MDSCs significantly reduced the clinical severity scores, which were associated with histopathological changes, and reduced inflammatory cell infiltration, epidermal hyperplasia, and fibrosis. Furthermore, hUCB-MDSCs decreased the serum levels of immunoglobulin E, interleukin (IL)-4, IL-5, IL-13, IL-17, thymus- and activation-regulated chemokines, and thymic stromal lymphopoietin. Additionally, they altered the expression of the skin barrier function-related proteins filaggrin, involucrin, loricrin, cytokeratin 10, and cytokeratin 14 and suppressed the activation of Df-restimulated T-cells via cell–cell interactions. hUCB-MDSCs promoted skin recovery and maintained their therapeutic effect even after recurrence. Consequently, hUCB-MDSC administration improved Df-induced AD-like skin lesions and restored skin barrier function. Our findings support the potential of hUCB-MDSCs as a novel treatment strategy for AD.
AB - Introduction: Previously, we achieved large-scale expansion of bone marrow-derived suppressor cells (MDSCs) derived from cluster of differentiation (CD)34+ cells cultured in human umbilical cord blood (hUCB) and demonstrated their immunomodulatory properties. In the present study, we assessed the therapeutic efficacy of hUCB-MDSCs in atopic dermatitis (AD). Methods: Dermatophagoides farinae (Df)-induced NC/Nga mice (clinical score of 7) were treated with hUCB-MDSCs or a control drug. The mechanisms underlying the therapeutic effects of hUCB-MDSCs were evaluated. Results and discussion: hUCB-MDSCs demonstrated immunosuppressive effects in both human and mouse CD4+ T cells. hUCB-MDSCs significantly reduced the clinical severity scores, which were associated with histopathological changes, and reduced inflammatory cell infiltration, epidermal hyperplasia, and fibrosis. Furthermore, hUCB-MDSCs decreased the serum levels of immunoglobulin E, interleukin (IL)-4, IL-5, IL-13, IL-17, thymus- and activation-regulated chemokines, and thymic stromal lymphopoietin. Additionally, they altered the expression of the skin barrier function-related proteins filaggrin, involucrin, loricrin, cytokeratin 10, and cytokeratin 14 and suppressed the activation of Df-restimulated T-cells via cell–cell interactions. hUCB-MDSCs promoted skin recovery and maintained their therapeutic effect even after recurrence. Consequently, hUCB-MDSC administration improved Df-induced AD-like skin lesions and restored skin barrier function. Our findings support the potential of hUCB-MDSCs as a novel treatment strategy for AD.
KW - atopic dermatitis
KW - inflammatory responses
KW - myeloid-derived suppressor cells
KW - skin repair
KW - T-cells
UR - http://www.scopus.com/inward/record.url?scp=85182806962&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2023.1263646
DO - 10.3389/fimmu.2023.1263646
M3 - Article
C2 - 38264643
AN - SCOPUS:85182806962
SN - 1664-3224
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1263646
ER -