Fig. 5

Intestinal barrier integrity is mediated by CCR2-expressing inflammatory monocytes in humans and mice. (A) Path analysis demonstrates that chronological age has a direct effect on circulating LPS levels and CCR2-expressing classical monocytes(CD14⁺CD16⁻) in humans. The amount of LPS in circulation is mediated by the monocytes in peripheral blood wherein the CCR2-expressing monocytes in circulation decreased with an increasing amount of circulating LPS. Effect estimates from the 100 simulations are shown in Table 4. In mice, (B)Ly6C^high monocyte prevalence (as a proportion of total CD45⁺ leukocytes) increased in the circulation of old wild-type females, but not old males. (C) Monocyte-derived CD4⁻TIM4⁻ colon macrophages have increased TNF expression in old mice. (D) Intestinal permeability, as measured by circulating FITC-dextran levels, increased in old wild-type females, but not old males or old Tnf^−/− females who are missing age-associated inflammation. (E) There was an inverse relationship between CCR2-expressing Ly6C^high monocyte and FITC-dextran in the circulation of females, but not males or (F) Tnf^−/− females. (G) Trans-epithelial electrical resistance (TEER) prior to- and following- administration of 2pg/mL TNF showed reduced barrier integrity following cytokine challenge