Cause found for lupus, which might lead to cure. Two cellular defects appear to drive the autoimmune disease

Good news!

"US researchers have found a mechanism that causes the life-threatening disease lupus.

The process opens up avenues for more direct treatment of the disease, which affects millions of people worldwide.

Lupus is an autoimmune condition that occurs when the immune system attacks the body’s ordinary cells. There currently isn’t any cure. ..."

"The autoimmune disease systemic lupus erythematosus — known as lupus — affects more than 1.5 million people in the U.S. ...
discovered a molecular defect that promotes the pathologic immune response in lupus and show that reversing this defect may potentially reverse the disease. ...
lead to insufficient activation of a pathway controlled by the aryl hydrocarbon receptor (AHR), which regulates cells’ response to environmental pollutants, bacteria or metabolites, a substance created when the body breaks down food, drugs, chemicals or its own tissue. Insufficient activation of AHR results in too many immune cells that promote the production of disease-causing autoantibodies. ..."

From the abstract:

"Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell–B cell interactions. Expansion of T follicular helper (TFH) and T peripheral helper (TPH) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE3. Human TFH and TPH cells characteristically produce high levels of the B cell chemoattractant CXCL13, yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4+ T cell phenotypes in patients with SLE, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4+ T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ TPH/TFH cell differentiation and promote an IL-22+ phenotype. Type I interferon, a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ TPH/TFH cells on a polarization axis opposite from T helper 22 (TH22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states."

Cause found for lupus, which might lead to cure

Scientists discover a cause of lupus and a possible way to reverse it (original news release) Two cellular defects appear to drive the autoimmune disease that affects more than 1.5 million Americans

Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus (no public access)

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