The orphan nuclear receptor NR4A3 is dispensable for resident memory CD8+ T-cell generation.

Different memory CD8+ T-cell subsets are generated following acute responses: central, effector and resident (Trm). CD8+ Trm cells established residency at the sites of infection and provide an efficient and rapid frontline defense against reinfection. The NR4A family members (NR4A1, NR4A2, and NR4A3) of orphan nuclear receptor are transiently expressed following TCR signaling and NR4As were shown to influence CD8+ T-cell response. Interestingly, Nr4a1, Nr4a2, and Nr4a3 have been reported to be transcribed by CD8+ Trm cells. NR4A1 and NR4A2 were shown to influence the generation of CD8+ Trm cells. However, evidence is still lacking for the contribution of NR4A3 during CD8+ Trm cell differentiation. In this study, we evaluated the role of NR4A3 in the differentiation and maintenance of CD8+ Trm cells. Our data demonstrate that in contrast to the other family members NR4A1 and NR4A2, NR4A3 is dispensable for the generation of CD8+ Trm cells at both epithelial and nonepithelial sites.