Increased CXCR3 Expression of Infiltrating Plasma Cells in Hunner Type Interstitial Cystitis.

Interstitial cystitis (IC) is a chronic bladder disease characterized by lower urinary tract symptoms such as urinary frequency, nocturia, urgency, and/or bladder pain, causing a deterioration in the sufferer’s quality of life1. To date, the pathophysiology of IC is largely unknown, although deficient barrier function of the urothelium, aberrant microvasculature, and neurogenic inflammation in the bladder have been suggested2,3,4,5. IC can be classified into multiple distinguishable phenotypes, with Hunner type IC (HIC), by the presence of the Hunner lesions on cystoscopy1,6. Histologically, HIC is a distinct inflammatory disease characterized by predominant infiltration of lymphoplasmacytic cells and denudation of the urothelium among IC7,8,9. We have examined these features by quantitative evaluation of cell numbers using novel image analysis software, confirming the accumulation of plasma cells in the lamina propria of the HIC bladder9. Furthermore, we have found a light-chain restriction of plasma cells in HIC cases, which suggests clonal expansion of B cells and possible involvement of immune responses in the persistent inflammation of HIC9. On the other hand, HIC is associated with up-regulated gene expression of CXCR3, a receptor for proinflammatory chemokines such as CXCL9, CXCL10, and CXCL1110,11. The CXCR3 pathway plays a crucial role in the persistent chronic inflammation seen, for example, in allergic and autoimmune diseases, because of its major chemoattractant properties in recruitment of inflammatory cells12,13,14,15. Here, to further characterize the inflammatory reaction in HIC, we examined CXCR3 expression of infiltrating immune cells in HIC specimens by immunohistochemistry using non-IC cystitis specimens as a control.