Immune system activation can result in persistent mood changes, exemplified by the increased incidence of anxiety and depression in people with immune disorders such as psoriasis, but the neural mechanisms that underlie immune system-mediated mood changes are poorly understood. Now, Lee et al. show, in a mouse model of psoriasis, that increased levels of cytokines such as IL-17A and IL-17C activate neurons of the basolateral amygdala (BLA) and increase anxiety-like behaviours, and that IL-10, acting on the same neuronal population, opposes these behavioural effects.

To investigate the link between immune activation and anxiety, the authors used a rodent model of psoriasis that recapitulates both the skin lesions and anxiety-like effects seen in the human condition. They focused on monitoring IL-17A, a cytokine released by T helper cells that is increased in human psoriasis and has been implicated in immune disorder-related anxiety and depression. The authors reasoned that reducing IL-17A signalling might attenuate both the skin lesions and the anxiety-like responses. They used a neutralizing antibody approach to reduce IL-17RA (the cognate receptor of IL-17A) in the periphery and found that psoriasis-like symptoms were attenuated as expected; paradoxically, though, there was an increase in anxiety-like behaviours, which also occurred with anti-IL-17RA treatment in naive mice. Serum levels of IL-17A and IL-1C, another cytokine that acts through IL-17RA, were increased following anti-IL-17RA treatment, so the authors hypothesized that the increase in anxiety-like behaviours might arise because of a central action of increased circulating IL-17A.