CIS Modulates Macrophage function

Here, we characterize the function of CIS in controlling macrophage activation, metabolic reprogramming, and inflammatory output. We show that CIS is rapidly upregulated in macrophages in response to cytokines and acts to restrain JAK?STAT signaling, thereby limiting the magnitude and duration of pro-inflammatory gene expression.

Loss of CIS results in heightened STAT1/STAT3 activation, and increased production of inflammatory mediators, whereas CIS expression skews macrophages toward an immunoregulatory phenotype. These findings establish CIS as a key regulator of macrophage functional plasticity and reveal its importance in maintaining immune homeostasis.