Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory genefamily. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cellactivation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We report herethat genetic ablation or blockade of PD-1H drastically promotes pulmonary inflammation with massive accumulationof eosinophils in a mouse model of experimental asthma, indicating a suppressive function of PD-1H in allergicinflammation. The loss of PD-1H led to elevated production of both innate cytokines (IL-6, MCP-1 and TNFα) andTh2 cytokines (IL-5 and IL-13) in the lung, indicating a critical role of PD-1H in suppressing the production ofairway inflammatory cytokines. In addition, the loss of PD-1H also impaired the expansion of systemic andpulmonary regulatory T cells during asthma induction. These findings support a critical role of intrinsic PD-1H inthe regulation of inflammatory responses to allergens. Finally, we showed that treatment with a PD-1H agonisticmonoclonal antibody reduced the severity of asthma, which was accompanied by suppressed lung inflammation.Our findings support PD-1H as a potential target and suggest a possible strategy for the treatment of allergicasthma in humans.
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