圖解：PD-L1的表達(dá)影響A型流感感染過程

【資料簡介】

有證據(jù)表明不變的自然殺傷T（iNKT）細(xì)胞在防護(hù)對(duì)抗A型流感病毒中發(fā)揮重要的作用。然而，抑制受體，程序性死亡因子1（PD1）及其配體，程序性死亡配體（PK-L）1和2在iNKT細(xì)胞上防護(hù)對(duì)抗A型流感病毒中的作用被證實(shí)。研究人員調(diào)查了在iNKT細(xì)胞上的這些共刺激分子的對(duì)流行性感冒的效應(yīng)。

文中研究結(jié)果證明iNKT細(xì)胞減少了對(duì)IAV的敏感性導(dǎo)致PK-L1表達(dá)的缺乏，并且在IAV后PD-L2是抑制有害炎癥應(yīng)答中PD-L2的存在具有重要作用。

原文摘要：

Lack of PD-L1 Expression by iNKT Cells Improves the Course of Influenza A Infection

Hadi Maazi,Abinav K. Singh,Anneliese O. Speak,Vincent Lombardi,Jonathan Lam,Bryant Khoo,Kyung Soo Inn,Arlene H. Sharpe,Jae U. Jung,Omid Akbari

There is evidence indicating that invariant Natural Killer T （iNKT） cells play an important role in defense against influenza A virus （IAV）. However, the effect of inhibitory receptor, programmed death-1 （PD-1）, and its ligands, programmed death ligand （PD-L） 1 and 2 on iNKT cells in protection against IAV remains to be elucidated. Here we investigated the effects of these co-stimulatory molecules on iNKT cells in the response to influenza. We discovered that compare to the wild type, PD-L1 deficient mice show reduced sensitivity to IAV infection as evident by reduced weight loss, decreased pulmonary inflammation and cellular infiltration. In contrast, PD-L2 deficient mice showed augmented weight loss, pulmonary inflammation and cellular infiltration compare to the wild type mice after influenza infection. Adoptive transfer of iNKT cells from wild type, PD-L1 or PD-L2 deficient mice into iNKT cell deficient mice recapitulated these findings. Interestingly, in our transfer system PD-L1−/−-derived iNKT cells produced high levels of interferon-gamma whereas PD-L2−/−-derived iNKT cells produced high amounts of interleukin-4 and 13 suggesting a role for these cytokines in sensitivity to influenza. We identified that PD-L1 negatively regulates the frequency of iNKT cell subsets in the lungs of IAV infected mice. Altogether, these results demonstrate that lack of PD-L1 expression by iNKT cells reduces the sensitivity to IAV and that the presence of PD-L2 is important for dampening the deleterious inflammatory responses after IAV infection. Our findings potentially have clinical implications for developing new therapies for influenza.