Abstract
Wnt/β-catenin signaling is relatively understudied in immunity and autoimmunity. β-catenin blocks inflammatory mediators and favors tolerogenic dendritic cell (DC) phenotypes. We show here that leukocytes from lupus-prone mice and SLE patients express diminished β-catenin transcriptional activity, particularly in myeloid cells, although other leukocytes revealed similar trends. Serum levels of DKK-1, an inhibitor under transcriptional control of Wnt/β-catenin, were also decreased in lupus-prone mice. Surprisingly, however, preemptive deletion of β-catenin from macrophages appears to have no effect on lupus development, even in mice with varying genetic loads for lupus. Although myeloid-specific loss of β-catenin does not seem to be important for lupus development, the potential role of this transcription factor in other leukocytes and renal cells remain to be elucidated.
Highlights
The Wnt/β-catenin or “canonical” Wnt pathway is a ubiquitous, conserved signaling pathway
To determine whether leukocyte β-catenin activity may contribute to serum β-catenin markers we observed in lupus, we isolated splenocytes from age-matched healthy B6 control and lupusprone Mrl-lpr mice
To determine whether leukocyte β-catenin activity is altered in patients with SLE, we isolated peripheral blood mononuclear cells (PBMCs) from healthy controls and SLE patients
Summary
The Wnt/β-catenin or “canonical” Wnt pathway is a ubiquitous, conserved signaling pathway. Β-catenin transcriptional activity is the result of canonical Wnt signaling (see S1 Fig). Soluble Wnt engages the seven membrane-spanning receptor Frizzled, activating Disheveled (Dsh). Disheveled blocks the beta catenin destruction complex, comprised of Axin, APC, and GSK-3. In the absence of Wnt signaling, this complex binds and phosphorylates β-catenin at Serine 33, Serine 37, and Threonine 41, leading to ubiquitination and degradation [4, 5]. In the presence of Wnt signaling Dsh inhibits this complex, allowing β-catenin to translocate to the nucleus and transcribe such targets as Axin-2, matrix metalloprotease 7, PPARδ, CD44, cyclin D1, and c-Jun [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
