34232 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 but healed skin due to the persistence of tissue resident memory T (Trm) cells responding to autoantigens/allergens. The survival of Trm cells is regulated by IL-7 and IL-15. We present a mouse model of recurrent contact hypersensitivity (CHS) and suggest a novel approach to the treatment of inflammatory skin diseases through inhibition of Trm cells thereby establishing long-term disease remission. Methods: Mice were sensitized on the abdomen with the allergen 2,4-dinitrofluorobenzene (DNFB) (day −5). Mice were challenged on day 0 with DNFB, and then rechallenged on days 30 and 60. Ear swelling was measured every 12 hours for 96 hours postchallenge. Ear skin was harvested 2 days (inflamed skin) and 15 days (healed skin) after each DNFB ear challenge (days 32, 45, 62 and 75). Results: Serial DNFB challenges produced progressively stronger peak CHS responses (1-month vs. 2-months re-challenge; 8.8 vs. 12.0 μm, *P < .05). The number of Trm cells and expression of IL-15-receptor increased in healed skin compared with inflamed skin. There were increases in Trm cell numbers, and Trm expression of IL-7- and IL-15-receptor in skin at 2 months compared with 1-month DNFB rechallenge. Conclusions: Repeat CHS inflammation via serial DNFB challenge lead to accumulation of Trm cells expressing IL-7 and IL-15-receptors in healed skin. We suggest that inhibition of IL-7/IL-15-receptors during disease quiescence to reduce Trm cell numbers, may be a novel strategy to prevent dermatitis recurrence and maintain long-term remission.