Shining light on the significance of NK cell CD56 brightness

CD56 is a fundamental marker in the determination of human natural killer(NK)cell subsets.The degree of CD56 expression is ubiquitously used to define human NK cell maturation,functional,and tissue-specific subsets,yet a unifying implication for the degree of CD56 expression in NK cells remains elusive.Peripheral blood(PB)-NK cells are dichotomized into CD56bright,which highly express CD56,and CD56dim,which have lower CD56 expression.Classically,CD56bright NK cells are considered to be a less mature,immunoregulatory subset with a greater propensity for cytokine production,whereas CD56dim are more mature with greater cytotoxic abilities.While PB-NK cells are primarily CD56dim with only a minor CD56bright population,NK cells in secondary lymphoid and other tissues are predominantly CD56bright.1 It has been shown that the interaction of CD56 with human fibroblast cells can promote the differentiation of CD56bright to CD56dim NK cells.2 However,considering the importance and the extent of use of this marker in NK cell biology,relatively little is known about how downregulation of CD56 contributes to NK cell maturation,what role the degree of CD56 expression plays in contexts separate from NK cell maturation,and whether CD56 has an active functional role in mature NK cells.

Remote hyperinflammation drives neurological disease via T-cell-mediated innate-like cytotoxicity

Inflammation is critical for the induction of immune responses to pathogens and other foreign substances.However,excessive local and systemic inflammation can have dire consequences beyond the original site of inflammation.A link between peripheral inflammation and neuropathology has been suggested for many diseases,including influenza infection,liver cirrhosis,and irritable bowel syndrome.1,2,3 Arguably,the vast majority of inflammatory diseases have been associated with deleterious neurological outcomes.Likewise,immunotherapies,such as CAR T-cell treatment,are known for their high risk of cytokine release syndrome and associated neurotoxicity.However,the mechanism behind this phenomenon of inflammation-induced neuropathology remains largely misunderstood.Preclinical evidence from animal models that accurately depict this phenomenon is limited;these models will be essential to uncover the role of peripheral inflammation in neurological complications of disease.Beginning to fill this gap in understanding,Zhou et al.reported critical evidence linking lymphocytes from the inflamed gut to neurological sequelae in infants with necrotizing enterocolitis(NEC).4 These results pave the way to understanding how peripheral inflammation can adversely enhance immune activation and result in downstream neurological disease.