TLR9/FCRL3 regulates B cell viability, apoptosis, and antibody and IL-10 production through ERK1/2, p38, and STAT3 signaling pathways.

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Date: Sept. 2022
Publisher: Springer
Document Type: Report; Brief article
Length: 316 words

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Keywords: Multiple sclerosis; FCRL3; B cell; IL-10; TLR9 Abstract B cells play a role in the progression of multiple sclerosis (MS) and are closely related to Fc-receptor like-3 (FCRL3), but little is known about FCRL3 in B cells and MS. Activation of TLR9 in B cells with CpG found that CpG promoted FCRL3 expression in a dose- and time-dependent manner. CpG significantly activated ERK1/2, p38, and STAT3 pathways, and FCRL3 overexpression further promoted the activation of these pathways, while FCRL3 siRNA significantly inhibited the activation of these pathways by CpG. CpG stimulation significantly promoted the viability of B cells, inhibited cell apoptosis, and enhanced the production of antibodies and secretion of IL-10 by B cells. FCRL3 siRNA blocked most of the above regulatory effects of CpG, but promoted the further production of antibodies by B cells. FCRL3 overexpression enhanced the pro-survival, anti-apoptotic, and IL-10-inducing effects of CpG, but inhibited the effect of CpG on promoting antibody production. After adding inhibitors of ERK1/2, p38, and STAT3 pathways, respectively, the effects of CpG on promoting cell viability, antibody production, and IL-10 secretion were significantly reduced, but the anti-apoptotic effect of CpG was only affected by the blockade of STAT3 pathway. In addition, FCRL3 regulated B cell antibody and IL-10 secretion mainly through its ITIMs. These results indicate that TLR9 activation affects B cell proliferation, apoptosis, antibody production, and IL-10 secretion by upregulating FCRL3 expression, and is associated with ERK1/2, p38, and STAT3 pathways. Therefore, FCRL3 may be an important target for the diagnosis and treatment of B cell--related diseases. Author Affiliation: (1) Department of Neurology, Yueyang People's Hospital, 414000, Yueyang, Hunan, China (2) Department of Neurosurgery, Yueyang People's Hospital, 414000, Yueyang, Hunan, China (3) Department of Pathology, Yueyang People's Hospital, 263 Baling East Road, Yueyang Tower District, 414000, Yueyang, Hunan, China (c) Article History: Registration Date: 08/29/2022 Received Date: 05/09/2022 Accepted Date: 08/15/2022 Online Date: 09/19/2022 Byline:

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Gale Document Number: GALE|A721886641