Cellular regeneration during recovery from RRV-induced pancreas involution.

<p>Pancreas sections from C57/B6 mice 7 days after inoculation with A) mock virus or B) RRV were immunostained for PCNA (red) and PDX-1 (green). PCNA-positive cells were increased following RRV, including scattered islet cells co-stained (yellow) for both PCNA and PDX-1. Magnification A: x10; B x20.</p

Correlation of blood glucose concentration with RV antigen in the pancreas.

<p>RV was quantified by ELISA 9 days after inoculation of C57/B6 mice with RRV.</p

Decrease in islet size and insulin content following inoculation with RRV.

<p>Pancreas sections from C57/B6 mice 2 days after inoculation with mock virus or RRV were fixed with 4% PFA and stained with DAPI for nuclei (blue) and with antibodies to insulin (green) and glucagon (red). Magnification x10.</p

Acute, TLR3-dependent involution of the pancreas following inoculation with RRV.

<p>A) Organ weights (% of total body weight) of C57BL/6 mice 3 days after inoculation with RRV (black circles) or mock virus (white circles) (n = 6 mice/group). B) Pancreas weights 2 days after inoculation of C57BL/6 mice with mock virus, RRV or inactivated RRV, or after i.p. injection of poly I:C (n = 6–10 mice/group), or after inoculation of TLR3 gene-targeted mice (n = 6 mice/group). Results in * denotes significant difference from mock virus controls (see text for P values).</p

Titers of rhesus rotavirus in tissues after inoculation of C57/Bl6 mice.

<p>* Titers are median values derived from fluorescence focus forming units on MA104 cells (3–6 mice/group).</p><p>Titers of rhesus rotavirus in tissues after inoculation of C57/Bl6 mice.</p

Inverse relationship between plasma insulin and blood glucose concentrations following inoculation with RRV.

<p>Plasma insulin and blood glucose were measured in cardiac puncture blood 3 days after inoculation of C57/B6 mice with mock virus (open circles) or RRV (solid circles).</p

Blood glucose concentrations following RRV or mock inoculation.

<p>Blood glucose was measured in individual C57BL/6 mice over 2 weeks following inoculation by gavage with 10⁶ FFU RRV (black circles; 6 females, 6 males) or mock virus (white circles; 4 females, 5 males). * P≤0.02; ** P<0.001. Results are representative of 3 separate experiments.</p

Increase in the number of TUNEL-positive cells in the pancreas following inoculation with RRV.

<p>Pancreas sections from C57/B6 mice 2 days after inoculation with mock virus (open circles) or RRV (solid circles) were scored for TUNEL-positive cells per section in 10 sections/mouse. Each point is the total number of TUNEL-positive cells per mouse; the mean and SD are superimposed.</p

The Closely Related CD103⁺ Dendritic Cells (DCs) and Lymphoid-Resident CD8⁺ DCs Differ in Their Inflammatory Functions

<div><p>Migratory CD103⁺ and lymphoid-resident CD8⁺ dendritic cells (DCs) share many attributes, such as dependence on the same transcription factors, cross-presenting ability and expression of certain surface molecules, such that it has been proposed they belong to a common sub-lineage. The functional diversity of the two DC types is nevertheless incompletely understood. Here we reveal that upon skin infection with herpes simplex virus, migratory CD103⁺ DCs from draining lymph nodes were more potent at inducing Th17 cytokine production by CD4⁺ T cells than CD8⁺ DCs. This superior capacity to drive Th17 responses was also evident in CD103⁺ DCs from uninfected mice. Their differential potency to induce Th17 differentiation was reflected by higher production of IL-1β and IL-6 by CD103⁺ DCs compared with CD8⁺ DCs upon stimulation. The two types of DCs from isolated lymph nodes also differ in expression of certain pattern recognition receptors. Furthermore, elevated levels of GM-CSF, typical of those found in inflammation, substantially increased the pool size of CD103⁺ DCs in lymph nodes and skin. We argue that varied levels of GM-CSF may explain the contrasting reports regarding the positive role of GM-CSF in regulating development of CD103⁺ DCs. Together, we find that these two developmentally closely-related DC subsets display functional differences and that GM-CSF has differential effect on the two types of DCs.</p></div

CD103⁺ DCs and CD8⁺ DCs differ in expression of costimulatory molecules, inflammasomes and TLR.

<p>(<b>A</b>) Cells of pooled cutaneous LNs from Langerin-EGFP mice and Langerin-EGFP/<i>CD103−/−</i> mice were analyzed. CD103⁺ DCs were identified as CD326⁻CD205⁺langerin⁺ within migratory DCs (mDC, CD11c^intMHC II^high); CD8⁺ DCs were identified as CD205⁺ CD8⁺ within cDCs (CD11c^highMHC II^int). Histograms show the expression of CD103 and langerin-EGFP by CD8⁺ and CD103⁺ DCs. For CD103 expression, CD8⁺ DCs (grey dot line) and CD205⁺CD11b⁻ migratory DCs (equivalent of CD103⁺ DCs, black dot line) from CD103−/− mice were included. (B) CD8⁺ and CD103⁺ DCs from B6 mice were analyzed for the expression of costimulatory molecules. (C&D) CD8⁺ and CD103⁺ DCs from B6 mice were sorted. RT-qPCR was performed for the indicated transcripts with 3 reference genes as controls. One of three repeated experiments is shown.</p