Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells. Matthew R Hepworth et al. Science 348, 1031 (2015)
Although the cause of IBD is not known, research indicates that an individual’s genetic susceptibility, external environment, intestinal microbial flora (bacteria) and immune responses are all involved and functionally related in some way.
The immune system is the body’s defence against infection. It is made up of a network of cells, tissues, and organs that work together to protect the body. T cells are one of the important cell groups which play a crucial role in defending our body against invaders.
The human gut contains trillions of (beneficial) bacteria. These play a role in nutrition, metabolism and immune cell function, and they also protect from infection from other bacteria and viruses. T cells know to ignore the body’s own beneficial bacteria in the intestine while they immediately try to recognize and remove any invaders they recognise as foreign.
The ability of T cells to learn how to differentiate beneficial from harmful bacteria takes place in the thymus and also in the gut. This learning process is essential to establish the tolerance to beneficial bacteria in the intestine which in turn maintains a healthy immune function. In a healthy person, tolerance to beneficial bacteria remains intact throughout his or her lifetime. However, some genetic risk factors or environmental insults may lead to altered tolerance, and as a result the immune system attacks beneficial bacteria in the intestine.
A research team at Weill Cornell Medical College in USA, has made a significant scientific breakthrough by showing how the immune system prevents chronic inflammation in the intestine. This group previously reported that cells known as innate lymphoid cells (ILCs) interact with T cells in the gut. These ILCs separate the immune system and intestinal beneficial bacteria by forming a physical barrier. In their latest study, researchers have found that ILCs directly educate T cells in the intestine and instruct them not to attack beneficial bacteria. A defect in the function of ILCs leads to intestinal inflammation.
The researchers reported that ILCs interact with T cells through the major histocompatibility complex class II (MHCII). The main function of MHCII molecules is to present processed antigens, which are derived primarily from foreign sources such as bacteria, to helper T cells. The purpose of this surveillance system is to stop the immune system running out of control and attacking the body’s own cells. The scientists found that loss of MHCII on the surface of ILCs is linked to pro-inflammatory cells in paediatric patients with Crohn’s disease in comparison to non-IBD controls. This impaired ILC3-MHCII interaction in paediatric Crohn’s disease suggests a possible role for alterations in this pathway in the onset or progression of IBD.
This study is pioneering research which details how the immune system learns to differentiate between self and harmful bacteria. Future investigations into eliminating pro-inflammatory T cells’ reactions may provide new therapeutic opportunities to treat IBD.