Differential control of Toll-like receptor 4-induced interleukin-10 induction in macrophages and B cells reveals a role for p90 ribosomal S6 kinases

作者：Sutavani Ruhcha V.; Phair Iain R.; Barker Rebecca; McFarlane Alison; Shpiro Natalia; Lang Stuart; Woodland Andrew; Arthur J. Simon C.^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2018, 293(7): 2302-2317.

DOI：10.1074/jbc.M117.805424

Increasing evidence has linked dysregulated interleukin (IL)-10 production by IL-10(+ve) B cells to autoimmunity, highlighting the importance of improving the understanding of the regulation of IL-10 production in these cells. In both B cells and myeloid cells, IL-10 can be produced in response to Toll-like receptor (TLR) agonists. In macrophages, previous studies have established that mitogen-and stress-activated protein kinases (MSKs) regulate IL-10 production via the phosphorylation of cAMP response element-binding (CREB) protein on the IL-10 promoter. We found here that although MSKs are activated in peritoneal B cells in response to TLR4 agonists, neither MSKs nor CREB are required for IL-10 production in these cells. Using a combination of chemical inhibitors and knockout mice, we found that IL-10 induction in B cells was regulated by an ERK1/2- and p90 ribosomal S6 kinase-dependent mechanism, unlike in macrophages in which p90 ribosomal S6 kinase was not required. This observation highlights fundamental differences in the signaling controlling IL-10 production in B cells and macrophages, even though these two cell types respond to a common TLR stimulus.

• 出版日期2018-2-16