AI Article Synopsis

  • Tertiary lymphoid structures (TLS) in kidneys of lupus-prone mice and SLE patients play a critical role in lupus nephritis development, and mesenchymal stem cells (MSCs) are involved in their formation.
  • Researchers found MSCs in kidney TLS and noted increased expression of specific genes related to inflammation during lupus nephritis in mouse models.
  • Human MSCs stimulated by pro-inflammatory cytokines promote the activation and proliferation of CD4+ T cells, suggesting that MSCs are essential in initiating kidney-specific TLS formation during chronic inflammation in lupus.

Article Abstract

Tertiary lymphoid structures (TLS) develop in the kidneys of lupus-prone mice and systemic lupus erythematosus (SLE) patients with lupus nephritis (LN). Here we investigated the presence of mesenchymal stem cells (MSCs) in the development of TLS in murine LN, as well as the role of human MSCs as lymphoid tissue organizer (LTo) cells on the activation of CD4+ T cells from three groups of donors including Healthy, SLE and LN patients. Mesenchymal stem like cells were detected within the pelvic wall and TLS in kidneys of lupus-prone mice. An increase in LTβ, CXCL13, CCL19, VCAM1 and ICAM1 gene expressions were detected during the development of murine LN. Human MSCs stimulated with the pro-inflammatory cytokines TNF-α and IL-1β significantly increased the expression of CCL19, VCAM1, ICAM1, TNF-α, and IL-1β. Stimulated MSCs induced proliferation of CD4 T cells, but an inhibitory effect was observed when in co-culture with non-stimulated MSCs. A contact dependent increase in Th2 and Th17 subsets were observed for T cells from the Healthy group after co-culture with stimulated MSCs. Our data suggest that tissue-specific or/and migratory MSCs could have pivotal roles as LTo cells in accelerating early inflammatory processes and initiating the formation of kidney specific TLS in chronic inflammatory conditions.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959845PMC
http://dx.doi.org/10.1038/s41598-018-26265-zDOI Listing

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