ECM1 controls Th2 cell egress from lymph nodes through re-expression of S1P1
Source:
Time: 2011-01-13
Recently, a research team, led by Prof. SUN Bing, from Shanghai Institute of Biochemistry and Cell Biology (SIBCB), discovered that ECM1 controls Type 2 helper (Th2) cell egress from lymph nodes through re-expression of S1P1.
Th2 cells are differentiated from naïve CD4+ helper T cells, which have a crucial role in adaptive immune responses. They are critically involved in inflammatory diseases such as allergies and asthma. Migration of Th2 cells into inflammatory tissues requires sphingosine-1-phosphate (S1P) interaction with the S1P receptor S1P1. Although T cell trafficking is crucial for immunological responses, the mechanisms controlling specific migration patterns remain unclear.
In Prof. Sun’s study, the researchers demonstrated that extracellular matrix protein-1 (ECM1) is highly and selectively expressed in Th2 cells. ECM1 deficiency caused impaired Th2 responses and reduced allergic airway inflammation in vivo. Functional analysis demonstrated that although the Th2 polarization of ECM1-deficient cells was unimpaired, these cells had a defect in migration and were retained in peripheral lymphoid organs. This was associated with reduced expression of Krueppel-like factor 2 (KLF2) and S1P1. The scientists also found that ECM1 could directly bind the interleukin-2 (IL-2) receptor to inhibit IL-2 signaling and activate S1P1 expression. Their data have identified a previously unknown function of ECM1 in regulating Th2 cell migration through control of KLF2 and S1P1 expression. Thus, ECM1 could be a potential target in treating allergies and asthma.
The research was published online in Nature Immunology on January 9th, 2011.
This work was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, the Chinese Academy of Sciences, and the Science and Technology Commission of Shanghai Municipality. (SIBCB)
AUTHOR CONTACT:
SUN Bing, Ph.D.
Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
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