Fiedler Katja, Kokai Enikö, Bresch Susanne, Brunner Cornelia
Ulm University, Institute of Physiological Chemistry D-89081 Ulm, Germany.
Am J Blood Res. 2013 May 5;3(2):124-40. Print 2013.
MyD88 was originally described as a primary response gene up-regulated during myeloid differentiation after IL-6 induction. Later, MyD88 was shown to be a key molecule necessary for IL1, IL18 and Toll-like receptor signaling. Since these receptors recognize abundantly produced cytokines during infection or molecular patterns of pathogens, MyD88 itself was suggested to be an important regulator of the first line of defense against invading pathogens, including the differentiation and maturation of myeloid cells. Here we describe that MyD88 is important for early and late hematopoietic events that occur independently of antigen under steady-state conditions. In MyD88-deficient mice the earliest alteration in hematopoiesis was found at the level of long-term hematopoietic stem cells. Moreover, we found that MyD88 influences not only the development of the myeloid lineage but also the differentiation of B cells. The B cell defect observed in Btk-deficient mice is further enhanced when both molecules, Btk and MyD88, are not expressed. Therefore, MyD88 affects myeloid as well as lymphoid hematopoiesis. Since Btk and MyD88 deficiencies influence differentially myeloid and lymphoid development, both molecules seem to act in different signaling pathways important for appropriate developmental events during myelo- and lymphopoiesis.
MyD88最初被描述为白细胞介素-6诱导后髓系分化过程中上调的一个初级反应基因。后来发现，MyD88是白细胞介素-1、白细胞介素-18和Toll样受体信号传导所必需的关键分子。由于这些受体在感染期间可识别大量产生的细胞因子或病原体的分子模式，因此有人提出MyD88本身是抵御入侵病原体第一道防线的重要调节因子，包括髓系细胞的分化和成熟。在此我们描述，在稳态条件下，MyD88对于独立于抗原发生的早期和晚期造血事件很重要。在MyD88缺陷小鼠中，最早的造血改变出现在长期造血干细胞水平。此外，我们发现MyD88不仅影响髓系谱系的发育，还影响B细胞的分化。当Btk和MyD88这两种分子都不表达时，Btk缺陷小鼠中观察到的B细胞缺陷会进一步加重。因此，MyD88影响髓系和淋巴系造血。由于Btk和MyD88缺陷对髓系和淋巴系发育的影响不同，这两种分子似乎在髓系和淋巴细胞生成过程中对适当发育事件很重要的不同信号通路中发挥作用。
