Disruption of the Epidermal Barrier Induces Regulatory T Cells via IL-33 in Mice

Abstract

Disturbance of the epidermal barrier by UVR is associated with the release of antimicrobial peptides and inflammatory cytokines for the purpose of a danger response. On the other hand, UVR causes immunosuppression via regulatory T cells (Treg) that limit the inflammatory reaction. The concurrent induction of antimicrobial peptides and Treg by UVR may represent a counter-regulatory mechanism in response to barrier disruption, preventing microbial superinfection and sensitization to contact allergens, respectively, both of which cross impaired epidermis more easily. Thus, using a model of murine contact hypersensitivity we examined if disruption of the epidermal barrier only initiates similar counter-regulatory mechanisms via the generation of Treg. Sensitization through tape-stripped skin induced a weaker contact hypersensitivity response than in control mice. This was due to the induction of antigen-specific Treg, as demonstrated in adoptive transfer and depletion experiments utilizing DEREG mice. Treg induction by tape stripping was linked to the expression of the alarmin IL-33, as blockade of IL-33 exacerbated contact hypersensitivity, whereas injection of IL-33 inhibited contact hypersensitivity and induced Treg. These results demonstrate that epidermal barrier disruption, in addition to danger signals, induces regulatory events that prevent exaggerated skin inflammation and that IL-33 appears to be critically involved in this process.

The Initiation of Th2 Immunity Towards Food Allergens

“…Allergic sensitization is usually achieved by causing a barrier disruption, typically through tape stripping (TS), prior to the placement of the allergen on the skin (sometimes through a patch) [ 108 , 109 , 110 ]. TS, which could be considered an external subverter, induces mechanical injury, damage, and local release of IL-33 [ 111 ], UA [ 59 ] and TSLP [ 108 , 112 , 113 ], etc. These alarmins are required for allergic sensitization through the priming of DCs to elicit a Th2-polarized immune response [ 114 , 115 ].…”

IL-33/regulatory T cell axis triggers the development of a tumor-promoting immune environment in chronic inflammation

“…These alarmins initiate type 2 allergic inflammation at barrier sites (7). They can activate Tregs, ILC2s, and mast cells upon epithelial damage in barrier organs (8,9). It is unknown if alarmins play a…”

Topical Adjuvant Application during Subcutaneous Vaccination Promotes Resident Memory T Cell Generation

“…instead of s.c. In addition, inhibitory mechanisms through the induction of regulatory T cells may also be induced by the TS process (30), and hence coapplication of the adjuvant and Ag may be needed to overcome this suppression.…”