Academician Dong Chen's research achievements have been shortlisted for 20 landmark advances in immunology in the past 20 years

To celebrate the magazine's 20th anniversary, NatureReviews Immunology screens 20 landmark advances in immunology over the past 20 years, including tumor immunity, immune metabolism, neuroimmunity, and host-microbiota immune interactions, and invites scientists who have made important contributions to introduce them. Dong Chen, academician of the Chinese Academy of Sciences and president of the Shanghai Institute of Immunotherapy Innovation, was successfully shortlisted for his research results.

In 2005, Dong Chen published a research paper in NatureImmunology, a top journal in the field of international immunology, and co-found a new class of helper T cells with Professor Casey T Weaver- Th17 cells, which broke the immunologists' understanding of only Th1 and Th2 types of helper T cells for more than 20 years. As a result, Dong Chen was invited to introduce the discovery of Th17 cells and wrote the article "Defining the TH17 Cell Lineage", which was published online on September 27, 2021.

It was generally believed that Th1 cells were closely related to autoimmune diseases until 2003, when studies found that Icos and Il23 deficiencies were able to significantly alleviate the mice's own immune response, a process that was closely related to reduced IL-17 secretion, but did not rely on Th1 cells. In 2005, Chen Dong and Casey T Weaver's group found that this group of IL-17-secreting cells is a third type of cell lineage developed from naïve T cells and independent of Th1 and Th2 cells. Casey T Weaver's group found that inhibiting Th1 and Th2 cells in vitro can enhance Th17 cell development, and IL-23 can further promote this process. In addition, Dong Chen's research group also found that this process still exists in mice with Th1 and Th2 deficiencies. At the same time, IL-17 can induce fibroblasts to secrete chemokines and metalloproteinases in in vitro tests, in vivo, overexpression of IL-17 can induce tissue inflammation, while blocking IL-17 inhibits the infiltration of immune cells into the central nervous system in mouse models with multiple sclerosis, and functionally establishes a close connection between such novel cells and tissue inflammation.

Taken together, the two studies identified a third class of CD4+ helper T cells, Th17 cells, which regulate tissue inflammation in infection and chronic inflammatory responses by secreting IL-17. Targeting Th17 cell-related molecules has been successful in several clinical trials, including the treatment of psoriasis and forced spondylitis.

However, not all autoimmune diseases can be treated with IL-17 neutralizing antibodies. Icos also play an important role in the development of follicular helper T cells (Tfh), which play an important role in mediating humoral immunity and antibody-mediated autoimmune diseases. Dong Chen and other research groups jointly identified the important function of BCL6 in regulating the development of Tfh cells, which was also listed as one of the 20 landmark advances, and was introduced in the article "Revealing T Follicle Helper Cells with BCL6".

The discovery of Th17 and Tfh cells has greatly promoted immunologists' understanding of immune diseases, especially autoimmune diseases, and has also promoted the development of new immune drugs.

It is understood that Dong Chen joined Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine in August 2020. On April 29 this year, the Shanghai Institute of Immunotherapy Innovation settled in Renji Hospital, with Dong Chen as the first president.

Column Editor-in-Chief: Gu Yong Text Editor: Huang Yangzi

Source: Author: Huang Yangzi