Estrogen signaling through ERα exacerbates intestinal inflammation selectively in males

---

Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B650
Abstract ID: 4345

Presenting Author:
Sarah McNeer , Graduate Student at Case Western Reserve Univ. Sch. of Med.

Abstract:

17β-estradiol (estrogen, E2) signals through two nuclear receptors, ERα and ERβ, to regulate gene expression in target cells, including immune cells. We previously showed that expression of ERβ was reduced in CD4+ T cells of Crohn’s disease patients, and deletion of ERβ in a mouse model of Crohn’s-like ileitis worsened inflammation selectively in females. These data led us to hypothesize that ERα-specific signaling (in the absence of ERβ) is pro-inflammatory in T cells, potentially in a sex-specific manner.

To test this, we used the CD45RB^high T cell transfer model of colitis to determine the inflammatory potential of T cells lacking expression of ERβ (ERβ-KO). In agreement with our hypothesis, transfer of male ERβ-KO T cells to sex-matched Rag2-/- recipients exacerbated colitis compared to transfer of wild-type (WT) cells. Despite worsened disease in male recipients of ERβ-KO T cells, there was no difference in the frequency or Th polarization status of CD4+ T cells recovered from the spleen, mesenteric lymph node, and colon. Further analyses showed a significant expansion of myeloid cells, particularly CD11b+F4/80+ macrophages, in recipients of ERβ-KO T cells. These findings suggest that ERα-specific signaling in T cells promotes recruitment or expansion of intestinal macrophages, contributing to worsened inflammation in vivo. Future studies will determine how signaling through ERα influences T cell interactions with these myeloid populations to exacerbate inflammation.