Skin Repair and Immunoregulatory Effects of Myeloid Suppressor Cells
from human cord blood on Atopic Dermatitis
Abstract
Background: In our previous study, we achieved large-scale
expansion of bone marrow-derived suppressor cells (MDSCs) derived from
CD34+ cells cultured in human umbilical cord blood (hUCB) and
demonstrated the immunomodulatory properties of these cells. This study
aimed to assess the therapeutic efficacy of hUCB-MDSCs in the treatment
of atopic dermatitis (AD). Methods: Dermatophagoides
farinae (Df)-induced NC/Nga mice (clinical score of 7) were
treated with hUCB-MDSCs or control drug. The mechanisms underlying the
therapeutic effects of hUCB-MDSCs were evaluated using dermatitis
scores, immunological parameters, skin histology, and skin barrier
function analysis. Results: hUCB-MDSCs demonstrated
immunosuppressive effects on both human and mouse CD4+ T cells.
hUCB-MDSC administration significantly reduced the clinical severity
scores and was associated with histopathological changes, such as
reduced inflammatory cellular infiltration, epidermal hyperplasia, and
fibrosis. hUCB-MDSC administration decreased the serum levels of IgE,
IL-4, IL-5, IL-13, IL-17, thymus- and activation-regulated chemokine
(TARC), and thymic stromal lymphopoietin (TSLP). Additionally,
hUCB-MDSCs altered the expression of skin barrier function-related
proteins such as filaggrin, involucrin, loricrin, and cytokeratin 10 and
suppressed Df restimulated T-cell activation through cell–cell
interactions. Furthermore, hUCB-MDSCs promote skin recovery and maintain
their therapeutic effect even after recurrence. Conclusions:
hUCB-MDSC administration improved Df-induced AD-like skin lesions and
led to the restoration of skin barrier function. Furthermore, hUCB-MDSC
treatment inhibited inflammatory responses and suppressed T-cell immune
function. Therefore, the results of this study support the potential for
hUCB-MDSCs as a novel treatment for AD.