001 Inhibition of tissue resident memory-T cells as a therapy for contact hypersensitivity

Background: Systemic therapy for eczema targets the immune system during active inflammation. Disease inevitably returns to previously inflamed skin due persistence of tissue resident memory T (Trm) cells responding autoantigens/allergens. The survival Trm is regulated by IL-15. We present a mouse model recurrent contact hypersensitivity (CHS) and suggest novel approach treatment inflammatory diseases through inhibition cells. Methods: C57BL/6 Mice were sensitized on abdomen with allergen 2,4-dinitrofluorobenzene (DNFB) (day -5), then challenged ear day 0. received peritoneal injections IL-15-receptor neutralizing antibodies, twice week four weeks, re-challenged DNFB 30 60. control group no antibodies. Ear swelling was measured every 12-hours 96-hours post challenge. harvested 2-days (inflamed skin) 15-days (healed after each re-challenge. Results: In group, serial challenges produced stronger peak CHS responses, significant increase at 2- months (p<0.05). number expression significantly increased in healed compared There increases cell 2-months 1-month re-challenge our inhibitor resulted less (p<0.05) reduced expressing IL-15 receptors control. Conclusions: IL-15-receptors accumulate following Inhibition disease quiescence prevents inflammation re-challenge, correlates reduction IL-15-receptors. This may be strategy prevent dermatitis recurrence maintain long-term remission.