Gut Homing T cells influence your immune response


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

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  • Ntalizumab is also effective in Crohn's disease by blocking alpha4 beta7 and preventing t-cell migration into intestinal villae. In MS blocking of alpha4beta1 by natalizumab prevents t-cell migration across the BBB. By stating that sequestration of t-cells in the gut is beneficial in preventing EAE this contradicts the proposed mechanism of action of natalizumab. Blocking of alpha4 beta1/7 is now detrimental as it allows reactive Th17 into the periphery. But the t-cells should still be blocked by natalizumab and should not increase EAE. ?

  • Good point steve s. Can i suggest you go onto the website at plos one and their is a comments post ask this very question and lets see if they have thought about it.
    I was once at a meeting when this hotshot immunologist who liked to make theories came up with a danger theory andd some one in audience said how can you have a transplant that is accepted for years whilst on immunosuppressive drugs and presumably the danger goes away. Stop the transplant drug and the kidney rejects within a week. heir response…..they were not interested in clinical stuff.

  • I’ve had conversations with my neurologist about people with MS respond to depleting either B-cell or T-cell. I had more relapses on Copazone than any DMT. Now Ocrevus is keeping my progression at bay for now. I wasn’t diagnosed with MS till I was 41 from a gestation. I’ve suffered from IBS, since I was 15. Correlation? Thank you for your work.

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