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Joseph Craft, MD

Paul B. Beeson Professor of Medicine (Rheumatology) and Professor of Immunobiology; Paul B. Beeson Professor of Medicine; Program Director, Investigative Medicine

Yale School of Medicine

Rheumatology

https://medicine.yale.edu/immuno/programs/joseph_craft.profile

Targeting Follicular Helper T Cells in Lupus

Immune cells called follicular helper T cells are enablers that allow B cells to produce autoantibodies (ANAs) that harm patients’ own tissues in lupus. A protein known as NFAT acts as a master switch to activate follicular T cells, turning the cells on and allowing them to function. We suspect that NFAT may work differently in follicular helper T cells in lupus, which could explain why B cells attack patients’ own tissues in the disease. To test our hypothesis, we will first analyze cells from healthy mice to determine how NFAT normally works. We will then test cells from mice and patients with lupus to see if and how NFAT functions changes in those with the disease. Drugs known as calcineurin inhibitors, now under study as treatments for kidney disease in lupus, inhibit NFAT and may prevent function of follicular helper T cells, although the precise mechanisms of how these drugs work are unclear. Our studies will test calcineurin inhibitors in mouse and human follicular helper T cells to determine whether they block the cells. The results of the proposed studies should help researchers better understand how T follicular cells may be improperly regulated in lupus and may point to new or improved therapies for lupus.

What this study means to people with lupus

“B cells damage patients’ own tissues, but they can’t launch their attacks without assistance from another type of immune cells called follicular helper T cells. We are trying to find out whether a certain protein allows these accomplice cells to behave differently in lupus and whether drugs under development will inhibit the function of the cells. A better understanding of how these partners operate can open new treatment avenues for lupus.”

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