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CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining
IL-10-Producing Regulatory T Cells
#MMPMID27036736
Evers BD
; Engel DR
; Böhner AM
; Tittel AP
; Krause TA
; Heuser C
; Garbi N
; Kastenmüller W
; Mack M
; Tiegs G
; Panzer U
; Boor P
; Ludwig-Portugall I
; Kurts C
J Am Soc Nephrol
2016[Nov]; 27
(11
): 3368-3382
PMID27036736
show ga
Kidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney
DCs belong to the CD11b(+) subset and promote crescentic GN (cGN). The function
of the CD103(+) subset, which represents <5% of kidney DCs, is poorly understood.
We studied the role of CD103(+) DCs in cGN using several lines of genetically
modified mice that allowed us to reduce the number of these cells. In all lines,
we detected a reduction of FoxP3(+) intrarenal regulatory T cells (T(regs)),
which protect against cGN. Mice lacking the transcription factor Batf3 had a more
profound reduction of CD103(+) DCs and T(regs) than did the other lines used, and
showed the most profound aggravation of cGN. The conditional reduction of
CD103(+) DC numbers by 50% in Langerin-DTR mice halved T(reg) numbers, which did
not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had
fewer CD103(+) DCs and T(regs) than Langerin-DTR mice but exhibited milder cGN
than did Batf3(-/-) mice presumably because proinflammatory CD11b(+) DCs were
somewhat depleted as well. Conversely, Flt3L supplementation increased the number
of CD103(+) DCs and T(regs), but also of proinflammatory CD11b(+) DCs. On
antibody-mediated removal of CD11b(+) DCs, Flt3L supplementation ameliorated cGN.
Mechanistically, CD103(+) DCs caused cocultured T cells to differentiate into
T(regs) and produced the chemokine CCL20, which is known to attract T(regs) into
the kidney. Our findings show that CD103(+) DCs foster intrarenal FoxP3(+) T(reg)
accumulation, thereby antagonizing proinflammatory CD11b(+) DCs. Thus, increasing
CD103(+) DC numbers or functionality might be advantageous in cGN.
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