John Mountz
University of Alabama at Birmingham, AL·Microbiology & Immunology
In systemic lupus erythematosus (SLE), or lupus, the immune system makes antibodies against the body's own tissues. A particular kind of B cell — the immune cell type that makes antibodies — appears in large numbers in lupus patients: cells marked by the transcription factor T-bet (a protein that switches on gene programs) together with the surface protein CD11c.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Pharmacology
- Topics
systemic lupus erythematosus
B cells
T-bet
- Grants
- 2 known grants, through Oct 2029
What they work on
- Determine which IL-4-induced tryptophan metabolic signals block TLR7-driven autoantibody-precursor B cells in vivo, comparing wild-type mice with mice lacking the B-cell enzymes IL4i1 and Ido1 or the metabolite sensor AhR.
- Test whether AhR is required to restrain T-bet+ B cells, using mice in which AhR is deleted only in B cells and chronically stimulated with the TLR7 ligand R848 to mimic viral-RNA-driven lupus activation.
- Map the route that generates AhR-activating ligands such as indole-3-pyruvic acid and kynurenine in B cells by comparing Il4i1-knockout and Ido1-knockout mice, and test whether giving these metabolites suppresses T-bet+ B cells in vivo.
- Determine, in B cells from SLE patients, whether AhR is needed for IL-4 to suppress DN2 B cells, an activated subset enriched in lupus, and whether altering IL4I1, IDO1 or their metabolites changes DN2 development.
- Identify which IL-4-induced metabolites best suppress age-related B cells, germinal center B cells and autoantibodies in BXD2 lupus-prone mice, using metabolomics and small-molecule screening to prioritize candidates.
More about the research
Most lupus research has chased the inflammatory signals that drive these cells. The work here takes the opposite angle: finding the natural "calming" signals that keep B cells in a resting, non-autoimmune state, and asking whether supplying those signals could become a gentler therapy. The central lead is the cytokine IL-4, a signaling protein that the lab has found keeps naive B cells quiet, and the small tryptophan-derived metabolites IL-4 causes B cells to make.
Why it matters
Current lupus drugs broadly suppress inflammation and carry real toxicity. By identifying natural tryptophan-derived metabolites that return B cells to a resting state, this work could point to orally available, more targeted treatments that curb autoantibody production in people with systemic lupus erythematosus without blanket immune suppression.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Marlies Meisel
University of Pittsburgh, PA·Microbiology & Immunology
Test whether checkpoint-inhibitor-response-associated gut bacteria convert dietary tryptophan into molecules that activate the aryl hydrocarbon receptor (AhR) and strengthen interferon-gamma-producing Tc1 CD8 T cells, in cell culture.
Erin Taylor
Augusta University, GA·Physiology
Test whether extra visceral fat worsens lupus and hypertension through harmful immune cells in fat, by surgically or pharmacologically depleting fat or its immune cells in female NZBWF1 mice.
Collynn Woeller
University of Rochester, NY·Microbiology & Immunology
Define the molecular steps by which the aryl hydrocarbon receptor, a chemical-sensing transcription factor, blocks activation of orbital fibroblasts — the connective-tissue cells behind the eye that turn into fat cells and scar-forming myofibroblasts in thyroid eye disease.
The school
University of Alabama at Birmingham: 45 labs on PI Pages, $866M a year on research, 166 research doctorates a year.
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