Abstract
Dendritic cells (DCs) are well known to be essential immunocytes involved in innate and adaptive immunity. DCs are classified as conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). Recently, the accumulation of pDCs in inflamed tissues and lymphoid tissues has been considered to be a possible contributing factor in the development of immunological diseases, but little is known about the pathophysiological roles of pDCs in immunological diseases. To date, many studies have demonstrated that many kinds of Kampo formulas can regulate immunological reactions in human immune diseases. Thus, we screened Kampo formulas to identify an agent that inhibits pDC migration. Furthermore, we investigated the therapeutic effects of these formulas on a murine DNFB-induced allergic contact dermatitis model. Bone marrow-derived pDCs (BMpDCs) were derived from the bone marrow cells of BALB/c mice in a culture medium with Flt3 ligand. The effects of Kampo formulas on BMpDC migration were evaluated by assessing the number, velocity, and directionality of BMpDCs chemotaxing toward the more concentrated side of a chemokine (C-C motif) ligand 21 (CCL21) gradient. The Kampo formulas that exerted inhibitory effects on pDC migration were orally administered to DNFB-induced allergic contact dermatitis model mice. Byakkokaninjinto reduced the number of migrated BMpDCs and suppressed the velocity and directionality of BMpDC migration in a chemotaxis assay. Gypsum Fibrosum and Ginseng Radix, which are components of byakkokaninjinto, obviously suppressed the velocity of BMpDC migration. Furthermore, Gypsum Fibrosum significantly suppressed the directionality of BMpDC migration. In DNFB-induced allergic contact dermatitis model mice, byakkokaninjinto markedly abrogated ear swelling in late-phase allergic reactions. In conclusions, byakkokaninjinto, which has an inhibitory effect on pDC migration, was able to prevent the occurrence of allergic contact dermatitis, suggesting that pDCs were involved in the onset of allergic contact dermatitis in the mouse model. Therefore, byakkokaninjinto is anticipated to be a therapeutic agent for disorders related to pDC migration.
Highlights
Dendritic cells (DCs) play a critical role in immune regulation
DCs have been divided into conventional dendritic cells and plasmacytoid dendritic cells. e bone marrow is the primary site of pDC production, and pDCs migrate through the circulation to the thymus, secondary lymphoid organs, and peripheral tissues
Among the 86 Kampo formula extracts, byakkokaninjinto significantly suppressed the migration of Bone marrow-derived pDCs (BMpDCs) from 25 minutes to 30 minutes at each time point (Figures 1(a) and 1(b), P < 0.05), and shimotuto significantly accelerated the migration of BMpDCs. e other 84 Kampo formula extracts did not show significant effects on BMpDC migration
Summary
Dendritic cells (DCs) play a critical role in immune regulation. In particular, DCs possess a strong ability to present antigens to CD4+ T cells. DCs, as versatile immunocytes, play roles in the induction of T-cell activation at the beginning of an immune response and in immune tolerance During these processes, DCs need to migrate to organs and tissues to exert their functions. Erefore, pDCs play essential roles in the pathogenic mechanism and defense mechanisms of many inflammatory skin disorders, including atopic dermatitis. Little is known about the effects of Kampo formulas on the function of DCs, a target for immunological diseases, even though DCs play a key role in immune responses. We investigated the effects of 86 Kampo formulas on pDC migration and demonstrated that byakkokaninjinto exerted therapeutic effects on an DNFBinduced allergic contact dermatitis model by inhibiting pDC migration
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Evidence-Based Complementary and Alternative Medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
