Expression of C-type lectin, SIGNR3, on subsets of dendritic cells, macrophages, and monocytes

Abstract

The C-type lectin SIGNR3 is a mouse homologue of human DC-SIGN, which shares carbohydrate-binding specificity with human DC-SIGN. However, the expression profile of SIGNR3 is largely unknown. To examine the expression of SIGNR3 in immune cells, we generated SIGNR3-specific mAb and investigated SIGNR3 expression in vivo. SIGNR3 was expressed on a fraction of MHC II(+) DCs and Mϕs in the dermis and CD115(+)Ly6C(int-low) monocytes in the blood and BM. In the LNs, SIGNR3(+) cells localized adjacent to PNAd(+) HEV-like vessels. They were also found in interfollicular regions in sLNs but not mLNs. Those SIGNR3(+) cells expressed CD11b and variable levels of CD11c and MHC II. As in LNs, SIGNR3 was expressed on a large proportion of the CD11b(+)CD11c(int-high) cells in the spleen. In the lung, SIGNR3(+) cells belonged to the CD11b(+)CD11c(int) population, and Mϕs in the airway and lung faintly expressed SIGNR3. When PKH67-labeled CD115(+)Ly6C(high) BM monocytes were transferred into normal recipients, they up-regulated SIGNR3 expression along with the decrease in Ly6C expression during the circulation and upon arrival at the peripheral LNs through HEV. In addition, CD11b(high)Ly6C(high) monocytes that entered sLNs differentiated into CD11b(+) DCs in a couple of days, whereas those in the spleen, mLNs, and lung differentiated into CD11c(int) monocytic cells. These results suggest that SIGNR3 is a new differentiation marker for myeloid mononuclear cells and indicate that some DCs, especially in the sLNs, are possibly replenished by Ly6C(high) monocytes.

Dectin-2 Is a Direct Receptor for Mannose-Capped Lipoarabinomannan of Mycobacteria

“…However, BMDCs lacking SIGNR1 were still capable of producing all cytokines tested at amounts comparable to those in WT BMDCs (Figure S4B). Another DC-SIGN homolog, SIGNR3, which is expressed in a limited population of myeloid cells (Nagaoka et al, 2010), was not detected in BMDCs (Figure S4C). Furthermore, forced expression of SIGNR3 in BMDCs did not increase Man-LAM-induced cytokine production (Figure S4D).…”

“…Thus, the characteristic cytokine production induced by Man-LAM seems to be determined by intrinsic signaling via Dectin-2 in DCs. Although Man-LAM-induced in vivo responses were also completely abolished in Clec4n -/mice, it is possible that SIGNR3 plays a role in Man-LAM responses in particular cells, such as dermal DCs, that express SIGNR3 (Nagaoka et al, 2010). Alternatively, these Man-LAM-binding molecules might promote the binding of myeloid cells to Man-LAM-bearing bacteria (Tanne et al, 2009), thereby leading to the efficient phagocytosis of mycobacteria.…”

The C-type Lectin Receptors Dectin-1, MR, and SIGNR3 Contribute Both Positively and Negatively to the Macrophage Response to Leishmania infantum

“…See also Figure S1 and Table S2. deletion of Clec7a (encoding Dectin-1) in Clec7a À/À mice to demonstrate its role in the elimination of C. albicans . As for SIGNR3, given that its expression is confined to myeloid mononuclear cells including different macrophage subsets (Nagaoka et al, 2010), we used Cd209d (encoding SIGNR3)-deficient mice that were instrumental to demonstrate its role in host defense against M. tuberculosis (Tanne et al, 2009). As depicted in Figures 2A and 2B, targeted deficiencies for Dectin-1 or MR in the myeloid compartment led to a higher parasite burden in the blood and spleen.…”

Monocyte trafficking in acute and chronic inflammation

“…One important question is how monocytes that enter the lymph node through the HEV, such as observed in L. major infection, gain access to antigen for presentation after they arrive and locally differentiate into DCs in the ensuing hours and days [58–61]. Inflamed lymph nodes (LNs) contain a population of CD11c lo CD11b + Gr1 + cells that phenotypically resemble monocytes, and appear to seed the LN through the HEV in a CCR2-dependent manner [15, 60, 62].…”