Oral

[O3-D-AM1-01] Dynamics of regulatory T cells in sublingual immunotherapy

〇Saka Winias¹, Toshinobu Kuroishi², Shunji Sugawara², Yukinori Tanaka³ (1. Div Oral Diag, Tohoku Univ Grad Sch Dent, 2. Div Oral Immunol, Tohoku Univ Grad Sch Dent, 3. Div Dent Anaesthesiol, Tohoku Univ Grad Sch Dent)

Keywords:Sublingual immunotherapy、Regulatory T cell、Gut microbiota

Sublingual immunotherapy (SLIT) is an allergen-specific treatment for allergic diseases, such as allergic rhinitis, through repeated inoculation of allergens under the tongue. We have previously shown that oral mucosal dendritic cells induce sublingual allergen-specific regulatory T cells (Tregs) in the draining submandibular lymph nodes (LNs), which can suppress allergic sensitization. However, it is not known where and how SLIT-induced Tregs are maintained. Therefore, in the present study, we investigated the dynamics of sublingual allergen-specific Tregs using a mouse model for SLIT. Sublingual administration of ovalbumin (OVA) on days 1 and 2 induced OVA-specific Tregs in submandibular LNs on day 5 and they were distributed in various LNs and spleen on day 12. Suppression of delayed-type hypersensitivity (DTH) to OVA by SLIT (twice per week for 3 weeks) was prevented by surgical removal of submandibular LNs before SLIT, suggesting the requirement of submandibular LNs for SLIT induction. Adoptive transfer of Tregs from submandibular and mesenteric LNs, but not skin-draining LNs or spleen, of mice treated with SLIT suppressed OVA-DTH in recipient mice. Surgical removal of mesenteric LNs, but not submandibular LNs, after SLIT prevented the suppressive effects of SLIT on subsequent OVA-DTH. Depletion of gut microbiota by antibiotics treatment after SLIT also prevented the suppression of OVA-DTH by SLIT. Collectively, these results suggest that SLIT-induced Tregs may be maintained in mesenteric LNs in a manner dependent on gut microbiota.