Without Adaptive Immunity, There’s a Cost to Responding STAT Eric M. Brown, Ramnik J. Xavier  Cell Metabolism  Volume 27, Issue 4, Pages 705-707 (April 2018) DOI: 10.1016/j.cmet.2018.03.011 Copyright © 2018 Terms and Conditions

Figure 1 A Working Model Describing the Impact of Adaptive Immunity on Innate Immune and Metabolic Function of Innate Lymphoid Cells and Small Intestinal Epithelial Cells In their study, Mao et al. (2018) described a new model which highlights signaling events employed by both innate and adaptive immune cells in response to the gut microbiota. In the presence of a functioning adaptive immune system (left panel), Th17 cells (pink) and Treg cells (purple) can override the IL-23-ILC3-IL-22-IEC gut circuit through IL-17A-mediated IEC signaling or a dampening of IL-23 production by CCR2+ monocytes (blue), respectively. In the context of a conventional Th17- and Treg-specific microbiota response, innate immune activation as measured by phosphorylated STAT3 (pSTAT3) is downregulated in IECs (beige) and ILCs (orange), and lipids are metabolized normally. When mice lack an adaptive immune system, CCR2+ IL-23 production is amplified, leading to ILC3 pSTAT3 activation (green), which then secretes a large amount of IL-22 (orange). This IL-22 is sensed by IECs, resulting in pSTAT3 activation and upregulation of a variety of innate immune genes. The energetic tradeoff of this IEC-specific innate immune activation is a disruption of lipid metabolism, leading to decreased fat accumulation and serum triglycerides. Therefore, adaptive immunity is crucial in promoting symbiotic host-microbe interactions (green arrow), and a lack of microbial adaptation results in dysregulated interactions (red arrow) and lipid metabolism defects. Cell Metabolism 2018 27, 705-707DOI: (10.1016/j.cmet.2018.03.011) Copyright © 2018 Terms and Conditions