Negative regulation of dendritic cell activation in psoriasis mediated via CD100–plexin‐B2

Abstract

Psoriasis is a chronic inflammatory skin disease in which dendritic cells (DCs) play a pivotal role by inducing Th1/Th17 immune responses; however, the regulation of DC activation in psoriasis remains largely unknown. Previously we found that the level of soluble CD100 was increased in sera of psoriasis patients, and CD100 promoted the activation of inflammasome in keratinocytes. In the present study, CD100 knockout mice were utilized for generation of imiquimod (IMQ)‐induced psoriatic dermatitis, with the result that skin inflammation in the early, but not late, phase of the psoriatic dermatitis was significantly exacerbated compared to that in wild‐type controls. This was attributed mainly to the deficiency of CD100 in hematopoietic cells. Bone marrow‐derived DCs, but not T cells or keratinocytes, from CD100 knockout mice produced significantly increased levels of IL‐1β, IL‐36, and IL‐23 upon stimulation with IMQ in a plexin‐B2‐dependent manner. Moreover, the surface level of plexin‐B2 on DCs of psoriasis patients was lower than that of healthy individuals, and CD100 attenuated IMQ‐induced production of IL‐1β and IL‐36 from monocyte‐derived DCs of psoriasis patients. Our results uncovered a negative regulatory mechanism for DCs activation in psoriasis, which was mediated via CD100–plexin‐B2 in a cell type‐ and receptor‐specific manner. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The Involvement of Semaphorins in the Pathogenesis of Skin Diseases

“…The result is an increase in the innervation of the skin by penetrating the fibers into the epidermis. Both the intensity of pruritus and the clinical concerns of psoriasis show a negative correlation with Sema3A mRNA expression [50]. However, not all studies support the correlation of Sema3A with nerve fiber density in patients with psoriasis and pruritus.…”

CD100 boosts the inflammatory response in the challenge phase of allergic contact dermatitis in mice

“…CD100 is broadly expressed by immune cells, including T cells, B cells, natural killer cells, and dendritic cells 32–36 . The ligands for CD100 are CD72 and Plexin B1/Plexin B2 expressed primarily in lymphoid tissues and nonlymphoid tissues, respectively 32,37–44 .…”

“…30,31 CD100 is broadly expressed by immune cells, including T cells, B cells, natural killer cells, and dendritic cells. [32][33][34][35][36] The ligands for CD100 are CD72 and Plexin B1/Plexin B2 expressed primarily in lymphoid tissues and nonlymphoid tissues, respectively. 32,[37][38][39][40][41][42][43][44] supports the activation of B cells and αβ T cells and its absence leads to defective activation of B and T cells.…”

Soluble Sema4D Level Is Positively Correlated with Sema4D Expression in PBMCs and Peripheral Blast Number in Acute Leukemia

“…Semaphorin 4D protein (Sema4D), also known as CD100, is expressed in T lymphocytes, B lymphocytes, dendritic cells, macrophages, neutrophils, and eosinophils [ 4 – 7 ]. It is expressed as a transmembrane protein, which can be cleaved by matrix metalloproteinase to release soluble Sema4D from cells [ 8 , 9 ].…”

“…Sema4D is involved in autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis [ 11 ]. It inhibits dendritic cell activation through interaction with Plexin-B2 in psoriasis [ 7 ] and promotes Th17 cell differentiation while inhibiting Treg cell differentiation in ankylosing spondylitis [ 12 ]. It also suppresses neutrophil activation in vasculitis [ 5 ].…”