Amphiregulin production from regulatory T cells does not require autocrine or paracrine feedback signaling 2260280

Abstract

Abstract Introduction Pneumonia triggers inflammatory responses followed by recovery and tissue repair. T regulatory (Treg) cells play a necessary role in coordinating the recovery process. Amphiregulin (Areg) is an epidermal growth factor receptor ligand that mediates the lung tissue-reparative function of Treg cells in mice. While IL-18 receptor and ST2 signaling promote Areg secretion from Treg cells, the signals required for optimal Areg production are unclear. Methods Mice were inoculated with influenza A with examination of lung and spleen Treg cells during the recovery phase of pneumonia. Results Here, we show in a model of influenza A pneumonia that Areg expression in lung and spleen Treg cells does not require paracrine or autocrine signaling following restimulation. Furthermore, optimal Areg detection required nuclear permeabilization, indicating that Areg may be localized within the nucleus. Conclusion These findings suggest that Treg cells are intrinsically programmed to produce Areg upon activation, independent of autocrine and paracrine signaling cues. Additionally, Areg may function to regulate transcriptional programs within the nucleus of Treg cells. Funding Source R01HL149883, P01HL154998 Topic Categories Cytokines and Chemokines and their Receptors (CCR)