Roles of B Cell-Intrinsic TLR Signals in Systemic Lupus Erythematosus

Abstract

Toll-like receptors (TLRs) are a large family of pattern recognition receptors. TLR signals are involved in the pathogenesis of systemic lupus erythematosus. Mouse and human B cells constitutively express most TLRs. Many B cell subpopulations are highly responsive to certain TLR ligation, including B-1 B cells, transitional B cells, marginal zone B cells, germinal center B cell and memory B cells. The B cell-intrinsic TLR signals play critical roles during lupus process. In this review, roles of B cell-intrinsic TLR2, 4, 7, 8 and 9 signals are discussed during lupus pathogenesis in both mouse model and patients. Moreover, mechanisms underlying TLR ligation-triggered B cell activation and signaling pathways are highlighted.

Lactobacillus fermentum CECT5716: a novel alternative for the prevention of vascular disorders in a mouse model of systemic lupus erythematosus

“…Furthermore, the immune system is intimately associated with TLR signals, which are involved in the pathogenesis of SLE (64). Our findings revealed that aortic mRNA levels of TLR-4 were higher in NZBWF1 mice compared with control mice.…”

The transcriptional repressor Gfi1 prevents lupus autoimmunity by restraining TLR7 signaling

“…Many different immune cell types are implicated in the development of SLE, of which DCs and B cells play a central role . cDCs and B cells are major antigen presenting cells that regulate T‐cell‐mediated autoimmunity, while pDCs drive disease by type I IFN production.…”

“…Marginal zone and B1 B cells have the capacity to respond to foreign antigens more rapidly than conventional B cells, providing early immune responses to blood‐borne pathogens, and both subsets are often altered in lupus prone mice . In various transgenic mice in the C57BL/6 background that develop lupus due to increased TLR7 signaling, such as mice that carry the Yaa locus , transgenic mice that overexpress TLR7 , mice that carry the Unc93B1‐D34A mutation , or TLR8‐deficient mice , the increased TLR7 signaling leads to reduced MZ B cell compartment, probably due to increased activation of the MZ B cells and their exit from this compartment .…”

The atypical IκB protein IκBNS is important for Toll‐like receptor‐induced interleukin‐10 production in B cells

“…In summary, our study proposes additional roles for I κ B NS in the development of IL‐10‐competent B cells and the modulation of B‐cell functions induced by TLRs. B‐cell‐intrinsic TLR signalling is also crucial for the generation and activation of autoreactive B cells . In this context, this unique signalling process could affect the pathogenesis of autoimmune diseases.…”

“…B-cell-intrinsic TLR signalling is also crucial for the generation and activation of autoreactive B cells. 46 In this context, this unique signalling process could affect the pathogenesis of autoimmune diseases. Hence, further studies will be required to elucidate the exact mechanism underlying TLR ligation-triggered B-cell activation and develop new strategies for immune disorders.…”