Stopping intestinal bacteria in their tracks

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The intestine contains the most immune cells in our body. Proper induction of intestinal immune cells plays a vital role in intestinal homeostasis, as the intestine is constantly exposed to various antigens such as bacteria and food.

POSTECH research team led by Professor Lee Seung-woo. Sookjin Moon, a candidate for the Department of Life Science, and Yunji Park, an assistant professor of research, first discovered a mechanism that regulates the differentiation of T cells (intraepithelial lymphocytes, IEL). Intestinal epithelial cells (IEC). These findings have recently been published Journal of Experimental Medicine (JEM), An authoritative journal of immunology, celebrating its 125th anniversary this year.

IELs present in the epithelium are cells that confront the outside of our body in layers of epithelial cells.In other words, IEL Immune cells Located around our body, it regulates the immune response when we encounter bacteria such as symbiotic microbes. Therefore, proper differentiation of IEL is essential for the regulation of intestinal immune homeostasis. However, the exact mechanism by which IEL distinguishes within the IEC layer was not well understood.

To this, the research team searched for specific environmental factors in the small distal part. Intestines Because IEL is concentrated in that part of the organ. Upon closer examination, IEC has determined that major histocompatibility complex class II (MHC II) and death ligand 1 (PD-L1) are induced by the microflora in the distal part of the small intestine transformed with CD4 + T cells. It became clear that it expresses. To IEL.

Through these molecules, IEC allows T cells to enter the IEC layer by providing antigen-specific T cell receptor (TCR) stimulation and programmed cell death protein 1 (PD-1) signaling. Induced maturity to IEL. In particular, PD-1 signaling induced the differentiation of CD4 + T cells into IEL by inhibiting the expression of ThPOK, the master transcriptional regulator of CD4 + T cells. This is a new role in PD-1 signaling that has never been reported.

In this study, T cell differentiation (a concept introduced in traditional immunology textbooks) induced by TCR stimulation and co-stimulation from professional antigen-presenting cells (APCs) is induced not only by APCs but also by histiocytes. It shows that you can do it.Even in the small intestine, IEC molecular expression Regional differences Between the proximal and distal regions due to environmental factors such as symbiotic microorganisms, this suggests that it plays an important role in the regulation of immune cells in each region. Small intestine..

“The way the IEC creates CD4 + IELs and puts them in the epithelial cell layer to control the invasion of gut flora is similar to training special agents and deploying them on the battlefield,” said Lee. Professor Seung-woo explained. “The fact that T cell differentiation is caused by IEC applies not only to the intestine, but to most tissues in our body. This is a promising sign for studying the role of tissues. cell.. ”

Immune cells monitor the intestine to prevent infection

For more information:
Sookjin Moon et al, niche-specific MHC II and PD-L1 regulate CD4 + CD8αα + intraepithelial lymphocyte differentiation. Experimental Medicine Journal (2021). DOI: 10.1084 / jem.20201665

Provided by Pohang University of Science and Technology (POSTECH)

Quote: Https: // Gut flora cessation on track (February 4, 2021) obtained on February 4, 2021

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