Fig. 1.

Recruitment of macrophages by nerve fibers in an estrogen-dependent manner. Upon the influence of estrogen, nerve fibers can secrete LIF, IL1 and PAP3, mediating the recruitment of macrophages. Estrogen can enhance the release of CSF1 and CCL2 to promote migration of macrophages toward peripheral nerves. The interaction of CCL2 and its receptors activates the polarization of macrophages. Synergistic effect of estrogen and TCDD can also induce the M2 polarization of macrophages through activation of the STAT3 and P38-MAPK pathway. LIF: leukemia inhibitory factor; IL1: interleukin 1; PAP3: pancreatitis- associated protein 3; CSF1: colony-stimulating factor 1; CCL2: C-C motif ligand 2; CCR: C-C motif chemokine receptor; TCDD: 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin; ER: estrogen receptor