Occludin Expression in Epidermal γδ T Cells in Response to Epidermal Stress Causes Them To Migrate into Draining Lymph Nodes

Abstract

Epidermal γδ T cells that reside in the front line of the skin play a pivotal role in stress immune surveillance. However, it is not clear whether these cells are involved in further induction of immune responses after they are activated in dysregulated epidermis. In this study, we found that activated γδ T cells expressed occludin and migrated into draining lymph nodes in an occludin-dependent manner. Epidermal γδ T cells in occludin-deficient mice exhibited impairments in morphology changes and motility, although they expressed activation markers at levels comparable to those in wild-type cells. Occludin deficiency weakened the induction of allergen-induced contact hypersensitivity, primarily as the result of the impaired migration of epidermal γδ T cells. Thus, occludin expression by epidermal γδ T cells upon activation in response to epidermal stress allows them to move, which could be important for augmentation of immune responses via collaboration with other cells.

Antibody-mediated delivery of VEGF-C potently reduces chronic skin inflammation

“…Furthermore, γδ T cells accumulate in the inflamed skin of K14-VEGF-A mice during CHS, and their numbers are increased in the lesional skin of human psoriasis patients (41). In addition, γδ T cells have been reported to migrate to draining lymph nodes in the context of skin inflammation, most likely via afferent lymphatic vessels (42). Therefore, a reduction in these disease-driving cells by increased lymphatic drainage may represent a likely mechanism for the antiinflammatory effects of F8-VEGF-C.…”

Get in Touch With Dendritic Epithelial T Cells!

“…In contrast, Occludin, a transmembrane enzyme normally found at tight junctions, is upregulated in activated DETC. Its expression has been associated with DETC rounding and with the ability of DETC to egress and home to draining lymph nodes (114). Similarly, DETC migration to, and accumulation in, skin draining lymph nodes has been reported in a CHS study (115).…”

γδ T cell migration: Separating trafficking from surveillance behaviors at barrier surfaces

“…Following activation by either stress or TCR engagement, DETCs upregulate the expression of the tight junction protein, occludin. 65 Surprisingly, loss of occludin expression adversely affected rounding as DETCs in occludin-deficient mice still showed dendrite extension even after irradiation. CD100 levels were similar in the presence or absence of occludin, suggesting that occludin expression may be regulated downstream of CD100.…”

“…CD100 levels were similar in the presence or absence of occludin, suggesting that occludin expression may be regulated downstream of CD100. 65 The importance of PALP localization beneath the keratinocyte junctional complex was further demonstrated by a study showing that binding of junctional adhesion molecule-like protein (JAML), a cell surface molecule on DETCs, to coxsackie and adenovirus receptor (CAR) expressed in the junction, functions as a co-stimulatory second signal. 66 Blocking of JAML/CAR interactions results in delayed wound healing.…”