Galectin-9 inhibits TLR7-mediated autoimmunity in murine lupus models
Santosh K. Panda, Valeria Facchinetti, Elisaveta Voynova, Shino Hanabuchi, Jodi L. Karnell, Richard N. Hanna, Roland Kolbeck, Miguel A. Sanjuan, Rachel Ettinger, Yong-Jun Liu
Santosh K. Panda, Valeria Facchinetti, Elisaveta Voynova, Shino Hanabuchi, Jodi L. Karnell, Richard N. Hanna, Roland Kolbeck, Miguel A. Sanjuan, Rachel Ettinger, Yong-Jun Liu
View: Text | PDF
Research Article Immunology Inflammation

Galectin-9 inhibits TLR7-mediated autoimmunity in murine lupus models

Abstract

Uncontrolled secretion of type I IFN, as the result of endosomal TLR (i.e., TLR7 and TLR9) signaling in plasmacytoid DCs (pDCs), and abnormal production of autoantibodies by B cells are critical for systemic lupus erythematosus (SLE) pathogenesis. The importance of galectin-9 (Gal-9) in regulating various autoimmune diseases, including lupus, has been demonstrated. However, the precise mechanism by which Gal-9 mediates this effect remains unclear. Here, using spontaneous murine models of lupus (i.e., BXSB/MpJ and NZB/W F1 mice), we demonstrate that administration of Gal-9 results in reduced TLR7-mediated autoimmune manifestations. While investigating the mechanism underlying this phenomenon, we observed that Gal-9 inhibits the phenotypic maturation of pDCs and B cells and abrogates their ability to mount cytokine responses to TLR7/TLR9 ligands. Importantly, immunocomplex-mediated (IC-mediated) and neutrophil extracellular trap–mediated (NET-mediated) pDC activation was inhibited by Gal-9. Additionally, the mTOR/p70S6K pathway, which is recruited by both pDCs and B cells for TLR-mediated IFN secretion and autoantibody generation, respectively, was attenuated. Gal-9 was found to exert its inhibitory effect on both the cells by interacting with CD44.

Authors

Santosh K. Panda, Valeria Facchinetti, Elisaveta Voynova, Shino Hanabuchi, Jodi L. Karnell, Richard N. Hanna, Roland Kolbeck, Miguel A. Sanjuan, Rachel Ettinger, Yong-Jun Liu

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (1.43 MB)

Advertisement