Systemic IL-12 burst expands intestinal T-lymphocyte subsets bearing the α₄ β₇ integrin in mice

• Published in: European journal of immunology Vol. 46; no. 1; pp. 70 - 80
• Main Authors: Pedrotti, Luciano P, Barrios, Bibiana E, Maccio-Maretto, Lisa, Bento, Allisson F, Sena, Angela A, Rodriguez-Galán, María Cecilia, Calixto, João B, Correa, Silvia G
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2016
• Subjects: Animals; Colitis - immunology; Flow Cytometry; Inflammation - immunology; Integrins - immunology; Interleukin-12 - immunology; Intestinal Mucosa - immunology; Lymph Nodes - immunology; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Peyer's Patches - immunology; T-Lymphocyte Subsets - immunology; Colitis; Systemic IL-12; Homing receptor; T cell; α4β7; Gut
• ISSN: 1521-4141
• DOI: 10.1002/eji.201545585

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.