Homeostatic regulation of T cell trafficking by a B cell–derived peptide is impaired in autoimmune and chronic inflammatory disease

Chimen M, et al. Nat Med 2015;21:467-75.

Speaker: Guan-Yu Chen (陳冠宇)                                                Time: 14:00~15:00, Sep 30, 2015

Commentator: Dr. Chrong-Reen Wang (王崇任醫師)         Place: Room 601

Abstract:

For the adaptive responses, the recruitment of lymphocyte into tissues plays an important role during inflammation. If lymphocyte recruitment is out of control, unregulated trafficking leads to chronic disease. In this study, the authors reveal a new activity of B cells that restricts the transendothelial migration (TEM) of T cell in response to adiponectin. Adiponectin is involved in metabolism, diabetes, and immunity, including the effect of leukocyte-endothelium interaction [1]. The authors found that the inhibition of T cell TEM by adiponectin is not direct, but is mediated through B cells. After adiponectin stimulation, B cells released a peptide, which they named PEPtide Inhibitor of Trans-Endothelial Migration or PEPITEM. PEPITEM bound to its receptor cadherin-15 on endothelial cells, and induced sphingosine-1-phosphate (S1P) biosynthesis, which was shown to regulate T cell migration previously [2]. Through S1P transporter SPNS2, S1P was translocated into extracellular space, and interacted with S1P receptors (S1PR1 and S1PR4) on the circulating T cells. The interaction of S1P and S1PR signalled to downregulate the affinity of LFA-1 and restrained T cell TEM. Furthermore, the authors identified that PEPITEM had the in vivo function by using the animal disease models. The PEPITEM pathway is not only limited in type 1 diabetes and rheumatoid arthritis, but also related with the age. In conclusion, there is a novel B cell-dependent pathway regulating the T cell trafficking with the potential to develop new therapeutic agents.

References:

1.     Ouedraogo R, et al. Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J Clin Invest 2007;117:1718–26.

2.     Ledgerwood LG, et al. The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics. Nat Immunol 2008;9:42–53.