The functional adaptation of effector Foxp3⁺ regulatory T cells to pulmonary inflammation

During infections, the timings of effector differentiation of pulmonary immune responses are of paramount importance, as pathogen persistence and unsuppressed inflammation can rapidly lead to a loss of function, increased frailty, and death. Thus, both an efficient clearance of the danger and a rapid resolution of inflammation are critical to host survival. We now know that tissue-localized FoxP3⁺ regulatory T cells, a subset of CD4⁺ T cells, are highly attuned to the type of immune response, acquiring unique phenotypic characteristics that allow them to adapt their suppressive functions with the nature of inflammatory cells. To achieve this, activated effector T_REG cells acquire specialized T_H 1, T_H 2, and T_H 17-like characteristics that allow them to migrate, survive, and time their function(s) through refined mechanisms. Herein, we describe how this process requires a unique developmental path that includes the acquisition of master transcription factors and the expression of receptors adapted to sense local danger signals that are found during pulmonary inflammation. In turn, we offer an overview of how these characteristics promote the capacity of local effector T_REG cells to proliferate, survive, and display suppressive strategies to resolve lung injury.