. Author manuscript; available in PMC: 2021 Aug 1.

Published in final edited form as: Nat Rev Gastroenterol Hepatol. 2021 Mar 17;18(8):571–587. doi: 10.1038/s41575-021-00423-7

Table 2 |.

Criteria for and examples of activated glia, reactive glia or gliopathy

Glial phenotype	Criteria	Examples from experimental evidence
Activated enteric glia	Response to physiological stimuli; normal signalling mechanisms whereby enteric glia monitor the activity of cells in the surrounding tissue; primarily enacts glial mechanisms that exert beneficial, homeostatic effects	Enteric glia exhibit activity encoded by intracellular Ca²⁺ signalling in response to neurotransmitters released by intrinsic (enteric)^{16,60,64,66,68,70,71,179} and extrinsic^12,18 neurons; enteric glial activation encoded by intracellular Ca²⁺ responses modulates enteric excitatory motor^10,14,17,60 and secretomotor¹¹ neurocircuits; enteric glia modulate local immune response in vitro and in vivo^{37,48,151,157}; enteric glia influence the maturation and differentiation of the intestinal epithelium in vitro^{46,104–106,180}
Reactive enteric glia	Response to pathophysiological perturbation of any severity; involves altered molecular composition, structure and/or function; changes undergone are progressive and depend on the type and severity of injury, glial subtype and specific molecular signals received; changes have the potential to alter glial activities through both gain and loss of functions that can be either beneficial or detrimental to the surrounding neural and non-neuronal cells	Enteric glia respond to intestinal inflammation^{12,13,62,116,148,155} and infection in vitro and in vivo^{22,148,170,172}; enteric glia undergo changes in GFAP expression, morphology, cytokine release and gene expression profile during intestinal inflammation in vitro and in vivo ^12,113,133; enteric glia contribute to neuron death during acute intestinal inflammation^13,147; enteric glia contribute to vagal anti-inflammatory effects on resident intestinal immune cells following intestinal injury^19,157; enteric glia influence visceral sensitivity through interactions with muscularis macrophages⁴⁸
Enteric gliopathy	Dysfunctional or maladaptive response and/or survival of glial cells; might be primary and result from genetic or acquired dysfunction emanating from glia, or secondary whereby glial dysfunction results from effects in the surrounding tissue; exerts detrimental effects that contribute to disease	Glial support of epithelial barrier homeostasis is impaired in Crohn’s disease in vitro^122,181; enteric glial networks are impaired and display dysfunctional responses in patients with Crohn’s disease^77,90