Throwing Intestinal Bacteria Off Track
Throwing Intestinal Bacteria Off Track
  • Reporter Lee Seung-ah
  • 승인 2021.02.28 01:33
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▲From left: Professor Seung-Woo Lee, Prof. Yunji Park, and Dr. Sookjin Moon
▲From left: Professor Seung-Woo Lee, Prof. Yunji Park, and Dr. Sookjin Moon

 

 

A research team led by Professor Seung-Woo Lee (LIFE), Sookjin Moon (LIFE Ph.D. Candidate), and Prof. Yunji Park (LIFE) revealed the mechanism by which intestinal epithelial cells (IECs) regulate the differentiation of T cells (intraepithelial lymphocytes, IELs). The study was published in the Journal of Experimental Medicine (JEM), an authoritative journal on immunology.
IELs work at the forefront of the human body, regulating immune responses by interacting with symbiotic bacteria. Therefore, the appropriate differentiation of IELs plays a vital role in the regulation of intestinal immune homeostasis. However, the precise mechanism by which IELs differentiate in the IEC layer was unknown.
Among the heterogeneous populations of IELs, there is a unique IEL subset CD4+CD8αα+ double-positive (DP) IELs, which is almost exclusively found in the small intestine and phenotypically and functionally distinct from the conventional CD4+ T cells in the periphery. Directing their attention to the fact that DP IELs are abundant in the distal part of the small intestine, the research team investigated specific environmental factors in the region. They discovered that the IECs expressed proteins such as major histocompatibility complex class II (MHC II) and the death-ligand 1 (PD-L1) induced by microbiota more in the distal part of the small intestine.
IECs induced DP IEL differentiation by providing antigen-specific T cell receptor (TCR) stimulation and PD-1 stimulation to CD4+ T cells upon their migration to the IEC layer. In particular, PD-1 stimulation induces the differentiation of CD4+ T cells into DP IELs by down-regulating the expression of ThPOK, a master transcription factor of CD4+ T cells, which is a new role of PD-1 stimulation that had not been previously reported.
A classical concept for T cell maturation in immunology is that professional antigen-presenting cells (APCs) induce T cell differentiation via TCR stimulation. However, this study shows an alternative pathway for T cell differentiation in which tissue cells can act as atypical APCs that induce T cell differentiation.
Meanwhile, the research was conducted with the support of the Organelle Network Research Center (ONRC) funded by the Science Research Center (SRC) program and the Mid-Career Researcher Program of the National Research Foundation of Korea.


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