Regulatory T (Treg) cells dampen immune responses to avoid excessive, deleterious inflammation in the context of autoimmunity, allergic reactions, and infection. Treg cells also impede anti-tumor immunity. Therefore, modulation of Treg cell activity is of great therapeutic potential for treating many debilitating inflammatory diseases and cancer. Recent studies have implicated a specialized tissue-resident Treg subset in limiting metabolic inflammation in the adipose tissue and in promoting repair of muscle injury. These Treg cells exhibit a unique transcriptional signature represented by high expression of the EGF family member amphiregulin (Areg), suggesting an additional role for Treg cells in tissue maintenance and remodeling. Whether Treg cells regulate tissue maintenance in broader settings, such as during infection and cancer progression, however, remains unknown. In the present study, we observed an Areg+ Treg subset in lung-infiltrating Treg cells following influenza infection. Selective ablation of Areg in Treg cells led to severe impairment of lung function and tissue damage without evident change in viral burden or antiviral response, indicating that the tissue maintenance function of Treg cells is distinct from their immune regulatory roles. Remarkably, we found that tumor infiltrating Treg cells highly expressed Areg. Since Areg is known to exert pleiotropic oncogenic activities, Areg production by Treg cells may be crucial for establishing the tumor microenvironment. Future studies will focus on: (1) Further examine the role for Areg+ Treg cells in tissue remodeling, during infection as well as cancer progression; (2) Characterize the Areg+ Treg cell subset; (3) Define the differentiation pathway of the Areg+ Treg cells. These studies will improve our understanding of both the immune and non-immune functions of Treg cells, and could provide new strategies for selectively targeting particular aspects of Treg cell function therapeutically in the treatment and control of inflammatory diseases and cancer progression.

Note:This abstract was not presented at the conference.

Citation Format: Wei Hu, Nicholas Arpaia, Paula D. Bos, Jesse Green, Alexander Rudensky. Tissue repair function of regulatory T cells during infection and cancer progression. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B081.