What question did this study set out to answer?

To examine whether the cytosolic DNA-sensing cGAS-STING pathway drives systemic autoimmunity in murine models of systemic lupus erythematosus (SLE) relative to endosomal TLR activation.

March 29, 2021Frontiers in ImmunologyOpen Access

cGAS-STING Pathway Does Not Promote Autoimmunity in Murine Models of SLE

View Full Paper

Ask AI

Bookmark

Authors

MMMona MotwaniBoston University JMJason D. McGowanUniversity of Massachusetts Chan Medical School JAJennifer AntonovitchUniversity of Massachusetts Chan Medical School

Discussion

Member takes

Implication

Preclinical study reveals that cGAS or STING deficiency exacerbates lupus manifestations in mice, indicating that this pathway constrains systemic autoimmunity.

Key Points

To examine whether the cytosolic DNA-sensing cGAS-STING pathway drives systemic autoimmunity in murine models of systemic lupus erythematosus (SLE) relative to endosomal TLR activation.
Evaluated the effects of cGAS or STING genetic deficiency in a chronic murine model of SLE induced by intraperitoneal pristane (TMPD) injection.
Generated cGAS-knockout mice on a pure MRL/Faslpr background using CRISPR/Cas9 and tested the requirement for endosomal TLR activation using Unc93B1-deficient crosses.
Administered adeno-associated virus (AAV)-delivered DNase I to TMPD-treated B6 mice to evaluate the role of extracellular or cytosolic DNA triggers.
TMPD-treated mice lacking cGAS or STING failed to show disease rescue, instead developing increased autoantibody levels and elevated proteinuria compared to wild-type controls.
CRISPR-generated cGAS-deficient MRL/Faslpr mice developed slightly exacerbated disease rather than clinical attenuation.
Concurrent deletion of Unc93B1 with cGAS or STING minimized systemic autoimmunity, while AAV-mediated DNase I delivery completely prevented TMPD-induced lupus.

Cite This Study

Motwani et al. (2021) studied this question.

synapsesocial.com/papers/6a9d73f730bdd6b10046e1c7 https://doi.org/10.3389/fimmu.2021.605930

View Full Paper

Ask AI

Bookmark

Implication

Preclinical study reveals that cGAS or STING deficiency exacerbates lupus manifestations in mice, indicating that this pathway constrains systemic autoimmunity.

cGAS-STING Pathway Does Not Promote Autoimmunity in Murine Models of SLE

Discussion

Member takes

Implication

Key Points

Cite This Study

cGAS-STING Pathway Does Not Promote Autoimmunity in Murine Models of SLE

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider