Systemic IL‐12 burst expands intestinal T‐lymphocyte subsets bearing the α₄β₇ integrin in mice

Abstract

The intestinal immune system is complex and displays unique anatomic and functional characteristics. Numerous immune cell subsets are located beneath the epithelial barrier and their activity is highly regulated. Using hydrodynamic shear of IL-12 cDNA to achieve systemic expression of IL-12 in mice, we evaluated the effect of a transient burst of this cytokine on the activation status of T cells from Peyer's patches (PPs), mesenteric lymph nodes (MLNs), and colonic lamina propria (LP). Following systemic IL-12 release, intestinal T lymphocytes became activated, exhibiting a CD44(high) CD62L(-) phenotype. After 5 days of the cytokine burst, the frequency of α4β7(+) CD4(+) and CD8(+) cells increased, and CD8(+) α4β7(+) cells mainly expressed T bet, a critical regulator of the Th1 differentiation program. The incremental increase in α4β7 expression involved the IL-12 receptor-signal transducer and activator of transcription (STAT)-4 axis, and occurred independently of IFN-γ, IL-4, IL-10, and TNF-α signaling. Moreover, IL-12 priming exacerbated the outcome of acute dextran sodium sulphate (DSS)-induced colitis with higher scores of weight loss, blood in stool, and diarrhea and lower hematocrit. Together, our findings demonstrate that systemic polarizing signals could effectively expand the number of effector cells able to home to the LP and contribute to local inflammation.

Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells

“…3). It is well known that IL-12 is the major cytokine for Th1 cell differentiation 68, 69 . In response to inflammations, both monocyte-derived DCs and macrophages produce IL-12 70–72 .…”

Ficolin‐A/2, acting as a new regulator of macrophage polarization, mediates the inflammatory response in experimental mouse colitis

“…(a), analysis of the gene expression array showed the fold changes of the inflammatory cytokines in livers between WT and FCN‐A KO mice. Recently, in the same way, Pedrotti et al . demonstrated that systemic cytokines could impair DSS colitis by priming lymphocytes and macrophages.…”

Large-Scale Integrative Analysis of Epigenetic Modifications Induced by Isotretinoin, Doxycycline and Metronidazole in Murine Colonic Intestinal Epithelial Cells

“…Furthermore, isotretinoin induced an anti-inflammatory immune cell profile in vitro and in vivo [21,28]. Pedrotti et al described local intestinal effects on lamina propria cells after systemic changes of IL-12 levels [40]. Thus, it is tempting to speculate that the previously described decrease of systemic IL-12p40 levels is affecting local IECs by up-regulating IL-12rb1 through a negative feedback mechanism that has been described for IL-7/IL-7R on T-cells [41,42].…”