CD69 acts downstream of interferon-a/b to inhibit S1P₁ and lymphocyte egress from lymphoid organs

Speaker: 呂秀菱                 Time: 13:10~14:00, May 10, 2006

Commentator: 王志堯 醫師       Place: Room 601

Abstract:

Circulating lymphocytes transiently stay in lymphoid organs is essential for activated lymphocyte proliferation and initiating adaptive immune response.Sphingosine 1-phosphate receptor-1 (S1P₁) is required for lymphocyte egress from lymphoid organs¹ and the ability is shut down transiently when lymphocytes are activated in lymphoid organs². In early stage, activation of lymphocytes needs several mediators of innate immune response, such as interferon -a/b ( IFN-a/b ), and can express some activation marker, like CD69. In this study³, treatment with the IFN-a/b inducer polyinosine polycytidylic acid (poly(I:C)) increased CD69 expression through IFN-a/b-receptor 1 ( IFNAR1 ) signaling, and decreased  the lymphocyte numbers in lymph and blood when S1P was added to activate S1P₁. In contrast, CD69^-/- cells retained normal S1P response, indicating that CD69 might be required for S1P₁ downmodulation. In addition, infection with lymphocytic choriomeningitis virus (LCMV) also induced IFN-a/b  production and resulted in similar extent as poly(I:C) induction. The authors also co-transfected retrovirus encoding CD69 and S1P₁ respectively into lymphocytes, and found abundant expression of CD69 whereas S1P₁ was downregulated and functionally inhibited. By co-immunoprecipitation of CD69 and S1P₁, results showed that CD69 formed a complex with S1P₁. Therefore, CD69 inhibited S1P₁ and the migration of lymphocytes, the authors suggested there should be other activating stimuli to restore the S1P₁ function.

Reference:

1.     Matloubian, M. et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427, 355–360 (2004).

2.     Sancho, D., Gomez, M. & Sanchez-Madrid, F. CD69 is an immunoregulatory molecule induced following activation. Trends Immunol. 26, 136–140 (2005).

3.     Shiow, R. et al. CD69 acts downstream of interferon-a/b to inhibit S1P₁ and lymphocyte egress from lymphoid organs. Nature 440, 540–544 (2006).