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. Author manuscript; available in PMC: 2025 Jul 23.
Published in final edited form as: Physiol Rev. 2025 Jan 15;105(3):1291–1428. doi: 10.1152/physrev.00034.2023

Figure 6. NOX2 regulation of NFκB is at the intersection between inflammatory and autoimmune disease.

Figure 6.

In macrophages, NOX2-derived oxidants prevent thioredoxin-1 (TRX1) reduction by thioredoxin reductase (TR-1) keeping TRX1 from entering the nucleus, thereby preventing NFκB-mediated pro-inflammatory cytokine production (TNFα, IL1 and IL6) and inflammatory disease (A). In contrast, regulatory T-cells (Tregs) play an essential role in protection against autoimmunity by suppressing T-cell responses. In NOX2-deficient Tregs, TRX1 levels accumulate in the nucleus and augment NFκB-mediated transcription of immunosuppressive cytokines (CD25, CD39 and CD73), which in turn, cause an increase in Treg-suppressive activity and the infiltration/proliferation of effector T cells, thus, inhibiting a hyperimmune/autoimmune response, and transplant rejection (B).