Related Experiment Video
Updated: Sep 28, 2026
Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
Published on: December 16, 2021
CD156 transgenic mice. Different responses between inflammatory types
Yasunori Higuchi1, Atsushi Yasui, Keiko Matsuura
1Department of Pathology, Oita Medical University, Oita, Japan. higuchi@oita-med.ac.jp
Abstract:
CD156 (ADAM8) is part of the ADAM family of proteins with the catalytic site consensus sequence of metalloprotease and disintegrins. To examine the role of CD156 in vivo, we generated mutant CD156 (eCD156) transgenic mice expressing the ectodomain of CD156 under the control of the alpha1-antitrypsin (AT) promoter. One of the transgenic mice designated ATMS2-TG18 expressed a 1.84 kb mRNA which was predicted to be a truncated CD156. The expression of the transgenic CD156 mRNA in ATMS2-TG18 mice was abundant in the liver and slight in kidney. Turpentine oil (TO) and lipopolysaccharide (LPS) markedly upregulated the expression. Soluble CD156 (sCD156) was produced constitutively, and increased after the treatment with TO. Casein-induced peritoneal leukocyte infiltration was significantly less extensive in ATMS2-TG18 than non-transgenic mice. The expression of L-selectin in neutrophils (PMN) from peripheral blood leukocytes (PBL) was more strongly downregulated in ATMS2-TG18 than non-transgenic mice, suggesting that L-selectin in PMN from ATMS2-TG18 mice was shed by sCD156. In contrast, oxazolone (Ox)-induced contact hypersensitivity reactions (CHR) were more marked in ATMS2-TG18 than non-transgenic mice. The expression of E-selectin mRNA was detected in inflammatory skin sites from ATMS2-TG18, but not non-transgenic mice, suggesting that sCD156 may activate the endothelial cells and lead to the upregulation of E-selectin. These results suggest that CD156 regulates leukocyte infiltration directly or indirectly.
Insights
Transgenic mice expressing CD156 (ADAM8) ectodomain showed altered leukocyte infiltration. Soluble CD156 (sCD156) reduced leukocyte infiltration but enhanced contact hypersensitivity, suggesting complex roles in immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- CD156 (ADAM8) is a metalloprotease-disintegrin protein involved in various biological processes.
- The specific in vivo functions of CD156, particularly its soluble form, remain incompletely understood.
Purpose of the Study:
- To investigate the in vivo role of CD156 by generating transgenic mice expressing its ectodomain.
- To elucidate the impact of soluble CD156 (sCD156) on leukocyte infiltration and inflammatory responses.
Main Methods:
- Generation of transgenic mice (ATMS2-TG18) expressing CD156 ectodomain under the alpha1-antitrypsin promoter.
- Analysis of CD156 mRNA expression in response to turpentine oil (TO) and lipopolysaccharide (LPS).
- Assessment of leukocyte infiltration (casein-induced) and contact hypersensitivity reactions (oxazolone-induced) in transgenic and non-transgenic mice.
Main Results:
- Transgenic mice exhibited constitutive production of sCD156, which increased upon TO treatment.
- Casein-induced leukocyte infiltration was significantly reduced in transgenic mice.
- Contact hypersensitivity reactions were enhanced in transgenic mice, with detected E-selectin mRNA expression in inflammatory skin sites.
- L-selectin expression on neutrophils was downregulated in transgenic mice, suggesting shedding mediated by sCD156.
Conclusions:
- Soluble CD156 (sCD156) plays a dual role in regulating leukocyte infiltration, inhibiting general infiltration while potentially promoting specific inflammatory responses.
- sCD156 may shed L-selectin from neutrophils and activate endothelial cells, leading to E-selectin upregulation.
- CD156 is a key regulator of leukocyte trafficking and inflammatory processes.
