Differential susceptibility between skin and vaginal mucosa in sensitization phase of allergic contact dermatitis in mice

Abstract

Introduction Mechanisms underlying skin sensitization in allergic contact dermatitis have been actively studied using the murine contact hypersensitivity (CHS) model. However, much less is known about sensitization at the vaginal mucosa (VM). Methods We developed a CHS model with VM sensitization and epicutaneous elicitation at the ear. We then examined the proliferation activity of lymphocytes, the frequencies of T cells and the differentiation of hapten‐specific T cells in draining lymph nodes (dLNs) after sensitization. Results Hapten‐specific CHS responses to 2,4‐dinitrofluorobenzene (DNFB), 2,4,6‐trinitrochrolobenzene, and oxazolone assessed by ear swelling suggested that the VM would be an inductive site of CHS to haptens. In the comparisons of CHS responses to each of the three haptens examined, the lower responses in VM‐sensitized mice were observed than skin‐sensitized mice (e.g., DNFB‐induced responses, −56%; p < .001, at 48 h after challenge). Consistent with the CHS responses, the DNFB‐induced proliferation of cells in dLNs examined by 5‐bromo‐2ʹ‐deoxyuridine assay was lower (−62%; p < .001) in VM‐sensitized mice than skin‐sensitized mice. On the other hand, between skin and VM sensitization, no significant differences were observed in the frequencies of interferon‐γ‐producing CD4+ and CD8+ effector, and regulatory T cells in dLNs after sensitization. We also observed no significant differences with respect to differentiation of hapten‐specific T cells based on the examination of cytokine production from dLN cells stimulated in vitro with 2,4‐dinitrobenzene sulfonate. Conclusion These findings suggested that the lower T cell proliferation after VM sensitization is important for the lower CHS responses with VM sensitization than skin sensitization.

Hapten sensitization to vaginal mucosa induces less recruitment of dendritic cells accompanying TGF‐β‐expressing CD206+ cells compared with skin

“…We previously reported that VM sensitization induced less ear swelling and fewer proliferating cells in dLNs than those in skin sensitization using a DNFB‐induced CHS model. 8 Consistent with the previous report, DC migration and recruitment after sensitization were limited in the VM compared with the skin (Figures 1 and 2 ). These observations indicated that sensitization ability in the VM might be lower than in the skin based on mechanism.…”

“…Compared with skin, there have been far fewer studies on contact allergy in the mucosae, especially in the vaginal mucosa (VM). We previously reported that in the comparison between skin and VM sensitization with 2,4‑dinitrofluorobenzene (DNFB), that preferentially induce Th1 responses, VM sensitization showed lower CHS including local ear swelling and T‐cell responses in the dLNs 8 . Differential DC status may contribute to differences in CHS responses between skin and VM sensitization.…”

CTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model mice

“…DNFB-sensitized mice were generated as previously described 29 , 30 . Mice were sensitized by applying 20 µL of 0.3% DNFB (v/v) (Sigma-Aldrich, St. Louis, MO, USA) dissolved in acetone/olive oil (4:1, v/v) (AOO) on the shaved dorsal skin on days 0, 1, and 2.…”