Zinc Finger AN1-Type containing 6 negatively regulates autoinflammation and autoimmunity

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Presentation Time: 04:45 PM - 05:00 PM
Abstract ID: 5638 - B

Presenting Author:
Wasif N Khan , Professor at Univ. of Miami Miller Sch. of Med.

Abstract:

Zinc Finger AN1-Type Containing 6 (ZFAND6) has been implicated in regulating NF-kB signaling and peroxisome biogenesis by interacting with polyubiquitinated proteins, but its physiological function remains unknown. We demonstrate that ZFAND6-deficient mice displayed normal appearance and behavior while harboring detectable alterations in the immune cell homeostasis and effector functions indicative of autoimmunity. ZFAND6-deficiency reduced marginal zone (MZ) B cells and increased Ly6^hi monocytes, T follicular helper (Tfh) and T peripheral helper (Tph) cells while potentiating spontaneous germinal center (GC) formation, and increasing serum IL-6, TNFa, and anti-SSA and anti-SSB autoantibodies. ZFAND6-deficient mice and isolated B cells exhibited much greater TLR7 and TLR9 stimulation-induced IL-6 response than the controls. We demonstrate that ZFAND6-deficiency exacerbated autoimmunity in the BBim^-/- mouse model of B cell-initiated Systemic lupus erythematosus (SLE) / Sjogren’s syndrome (SS). Thus, ZFAND6-mediated signaling is a key regulatory mechanism to restrain TLR-mediated inflammation in B cells and innate cells to limit autoimmune disease.