کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2865849 | 1573378 | 2015 | 9 صفحه PDF | دانلود رایگان |
Tertiary lymphoid structures (TLSs) in chronic inflammation, including rheumatoid arthritis (RA) synovial tissue (ST), often contain high endothelial venules and follicular dendritic cells (FDCs). Endothelial cell (EC)–specific lymphotoxin β (LTβ) receptor signaling is critical for the formation of lymph nodes and high endothelial venules. FDCs arise from perivascular platelet-derived growth factor receptor β+ precursor cells (preFDCs) that require specific group 3 innate lymphoid cells (ILC3s) and LTβ for their expansion. Previously, we showed that RA ST contains ECs that express NF-κB–inducing kinase (NIK), which is pivotal in LTβ-induced noncanonical NF-κB signaling. We studied the relation between NIK+ ECs, (pre)FDCs, and ILC3s with respect to TLSs in RA ST. TLS+ tissues exhibited a significantly increased expression of genes involved in noncanonical NF-κB signaling, including NIK, and immunohistochemical analysis revealed that NIK was almost exclusively expressed by ECs. ILC3s were present in human RA ST in very low numbers, but not differentially in TLS+ tissues. In contrast, TLS+ tissues contained significantly more NIK+ ECs and perivascular platelet-derived growth factor receptor β+ preFDCs, which correlated significantly with the quantity of FDCs. We established a strong link between NIK+ ECs, (pre)FDCs, and the presence of TLSs, indicating that NIK+ ECs may not only be important orchestrators of lymph node development but also contribute to the formation of TLSs in chronic inflammation.
Journal: The American Journal of Pathology - Volume 185, Issue 7, July 2015, Pages 1935–1943