Berer K, Boziki M, Krishnamoorthy G. Selective accumulation of pro-inflammatory T cells in the intestine contributes to the resistance to autoimmune demyelinating disease. PLoS One. 2014 Feb 4;9(2):e87876.
Myelin-specific, pro-inflammatory TH17 cells are widely regarded as the drivers of experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple sclerosis (MS). The factors, responsible for the generation and maintenance of TH17 cells as well as their participation in the pathogenic cascade leading to the demyelinating disease, have been studied extensively. However, how these harmful autoreactive cells are controlled in vivo remains unclear. By comparing TCR transgenic mice on a disease susceptible and a disease resistant genetic background, we show here that pathogenic TH17 cells are sequestered within the intestine of spontaneous EAE resistant B10.S mice. Disease resistant B10.S mice harbored higher frequencies of TH17 cells in the intestine compared to EAE susceptible SJL/J mice. Moreover, transferred TH17 cells selectively migrated to intestinal lymphoid organs of B10.S mice. The sequestration of TH17 cells in the gut was partially dependent on the gut homing receptor α4β7-mediated adhesion to the intestine. Administration of α4β7 blocking-antibodies increased the peripheral availability of TH17 cells, resulting in increased EAE severity after immunization in B10.S mice. Together, these results support the concept that the intestine is a check-point for controlling pathogenic, organ-specific T cells.
There is a growing momentum about the effects of gut bacteria on shaping the immune response. This study suggests that part of the genetic resistance of certain mouse strains B10.S (resistant) verses SJL (susceptible) in studies using transgenic mice where all t cells expressed the same myelin recognition molecule they suggests that this relates to cells being sequestered into the gut and if you block the adhesion molecule alpha4,beta7 also known as LPAM-1, it resulted in increase EAE, which is interesting as in EAE target of the LPAm-1 is in blood vessels in EAE whih express mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) in the brain. Anyway more focus on the gut and more armunition for the microbiome transplants