Ovariectomy increases paclitaxel-induced mechanical hypersensitivity and reduces anti-inflammatory CD4+ T cells in the dorsal root ganglion of female mice

Abstract

Chemotherapy is often dose limiting due to the emergence of a debilitating neuropathy. IL-10 and IL-4 are protective against peripheral neuropathy, yet the cell source is unknown. Using flow cytometry, we found that naive females had a greater frequency of anti-inflammatory CD4+ T cells in the dorsal root ganglion (DRG) than males. In response to paclitaxel, females had reduced hypersensitivity and a greater frequency of anti-inflammatory CD4+ T cells (FoxP3, IL-10, IL-4) in the DRG than ovariectomized and male mice. These findings support a model in which estrogen promotes antiinflammatory CD4+ T cells in female DRG to suppress peripheral neuropathy. HighlightsO_LICD4+ T cells are present in the dorsal root ganglion of naive and paclitaxel-treated male and female mice. C_LIO_LINaive female mice have a higher frequency of CD4+ T cells in the dorsal root ganglion compared to ovariectomized female and male mice. C_LIO_LIPaclitaxel induces more severe mechanical hypersensitivity in ovariectomized female and male mice compared to estrogen-competent female mice. C_LIO_LIPaclitaxel increases pro- and anti-inflammatory CD4+ T cells in the dorsal root ganglion of both male and female mice, but the increase in anti-inflammatory T cells is more robust in female mice. C_LIO_LIOvariectomy reduces cytokine-producing CD4+ T cells in the dorsal root ganglion and prevents the PTX-induced increase in cytokine-producing CD4+ T cells in the dorsal root ganglion. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/476262v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@235050org.highwire.dtl.DTLVardef@6decadorg.highwire.dtl.DTLVardef@cd7b1borg.highwire.dtl.DTLVardef@4d5b43_HPS_FORMAT_FIGEXP M_FIG Image created with Biorender.com C_FIG