CD161 defines a functionally distinct subset of pro-inflammatory NK cells. Frontiers
Natural killer (NK) cells are the most classical population of innate lymphoid cells, expressing a heterogeneous repertoire of germline-encoded receptors that allows them to distinguish infected or stressed cells from healthy cells. CD161 is a C-type lectin-like receptor expressed on the majority of natural killer (NK) cells; however, the significance of CD161 expression on NK cells has not been comprehensively investigated. Recently, the author-group has found that CD161 expression identifies a transcriptional and innate functional phenotype that is shared across various T cell populations.
In the current work, Kurioka et al. demonstrated using mass cytometry and microarray experiment that this functional phenotype extends to NK cells. CD161 marks NK cells that have retained the ability to respond to innate cytokines during their differentiation, and is lost upon cytomegalovirus-induced maturation in both healthy and human immunodeficiency virus (HIV)-infected patients. These pro-inflammatory NK cells are present in the inflamed lamina propria where they are enriched for integrin CD103 expression.
In summary, the study has shown that CD161 is a marker of NK cell function, particularly marking pro-inflammatory NK cells, which is expressed on all NK cells in cord blood, downregulated upon proliferation, and lost upon CMV-induced terminal differentiation. CD161 expression on CD56dim NK cells marks cells that have retained the capacity to respond to inflammatory cytokines alone. CD161, thus, identifies “innate” cells within both NK cells and CD161bright T cell family, previously described, with shared innate-type responses that are independent of receptorligation.