Figure 3. Cellular mechanisms for SPMs in lung anti-inflammation and pro-resolution.
During a self-limited inflammatory response, resolution of inflammation is an active process governed by specialized pro-resolving mediators (SPMs) that transmit both anti-inflammatory (red) and pro-resolving (blue) actions to leukocytes and tissue-resident cells. This class of endogenous immunoresolvents induces an anti-inflammatory response by inhibiting granulocyte migration and activation, disrupting sensory neuron activation and dampening cytokine production by a variety of structural cells, including epithelial cells, endothelial cells and fibroblasts. SPMs have a multipronged action to regulate sentinel innate lymphoid cells to decrease cytokine and increase amphiregulin production. These mediators also promote resolution by inducing regulatory T cells to control innate lymphoid cells, stimulating natural killer cells to trigger granulocyte apoptosis and engaging macrophages in a non-phlogistic manner to engulf bacteria and noxious stimuli, and clear apoptotic cells by efferocytosis. IL-5, interleukin-5; O2−, superoxide; TNF, tumour necrosis factor; TRPV1, transient receptor potential cation channel subfamily V member 1.