**9. Conclusions**

In this review, we summarize the aberrant activation of NF-κB in pSS, clearly demonstrating that NF-κB has a crucial role in the pathogenesis of pSS, since it promotes chronic inflammation. NF-κB, through intrinsic SGEC activation, regulates sophisticated feedback circuits in pSS that comprise all elements of the cellular immune response. Since NF-κB and members of its signalling pathways regulate cellular activity from DNA transcription to translation into proteins, efficient and properly controlled NF-κB signalling is important during physiological immune homeostasis. In fact, the integrity of the signal triggered by NF-κB is essential in preventing the onset of pSS autoimmune disease. It is noteworthy that the significance of NF-κB activation in pSS suggests that inhibition of this signalling pathway could provide novel strategies for the prevention and treatment of the SGs dysfunction characterizing pSS. New future perspectives suggest, for example, the use of IKKε inhibitors for the treatment of pSS, repressing downstream NF-κB signalling activation. Furthermore, great attention is now being paid to the modulation of NF-κB activity and expression of NF-κB target genes through an IκBα-mediated negative feedback mechanism. Hopefully, as our understanding of the regulation of the NF-κB pathways increases, insights into a better design of drugs that can effectively target NF-κB for the prevention and treatment of pSS may be gained.

**Author Contributions:** All authors conceived of the presented idea and approved the final version of the manuscript. M.S. and S.L. collected the data reported in the study and take responsibility for their integrity. D.R. performed a critical reading of this review. All authors have read and agreed to the published version of the manuscript.

**Funding:** No external funding was involved in this review.

**Acknowledgments:** We are grateful to the professional scientific text editor M.V.C. Pragnell, B.A., for critical reading of the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.
