Phenotypic and functional alterations of pDCs in lupus-prone mice

Abstract

Plasmacytoid dendritic cells (pDCs) were considered to be the major IFNα source in systemic lupus erythematosus (SLE) but their phenotype and function in different disease status have not been well studied. To study the function and phenotype of pDCs in lupus-prone mice we used 7 strains of lupus-prone mice including NZB/W F1, NZB, NZW, NZM2410, B6.NZMSle1/2/3, MRL/lpr and BXSB/Mp mice and C57BL/6 as control mice. Increased spleen pDC numbers were found in most lupus mice compared to C57BL/6 mice. The IFNα-producing ability of BM pDCs was similar between lupus and C57BL/6 mice, whereas pDCs from the spleens of NZB/W F1 and NZB mice produced more IFNα than pDCs from the spleens of C57BL/6 mice. Furthermore, spleen pDCs from MRL-lpr and NZM2410 mice showed increased responses to Tlr7 and Tlr9, respectively. As the disease progressed, IFN signature were evaluated in both BM and spleen pDC from lupus prone mice and the number of BM pDCs and their ability to produce IFNα gradually decreased in lupus-prone mice. In conclusion, pDC are activated alone with disease development and its phenotype and function differ among lupus-prone strains, and these differences may contribute to the development of lupus in these mice.

MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice

“…Consistently, splenic and lymph node pDCs in lupic NZB/W F1 mice have also been shown to display elevated expression of costimulatory molecules, including CD40 and CD86 in pDCs when compared with mice prior to disease onset [41,42], suggesting that the BM-derived pDCs bear similarities to the peripheral circulating pDCs. Similarly, a recent report by Zhou et al has also demonstrated in disease NZB/W F1 mice a higher expression of MHC-II and CD80 in ex vivo splenic and BM pDCs when compared with pre-disease mice [30]. Likely, these peripheral pDCs in disease mice have been continuously exposed to and stimulated by TLR7 stimulating immune complexes in vivo , thus leading to the hyperactivated phenotypes upon ex vivo examination.…”

Expanding the B Cell-Centric View of Systemic Lupus Erythematosus

“…The most current research has shed light into the role for pDCs during the initiation of TLR-mediated inflammation [64]. Various deficiencies that result in depletion of pDCs in mouse models show that when pDCs are absent, the severity of lupus disease is greatly diminished.…”

Plasmacytoid dendritic cells from parent strains of the NZB/W F1 lupus mouse contribute different characteristics to autoimmune propensity

“…pDCs of different mouse strains may have different properties . Here we investigated the pDC difference among NZB, NZW and NZB/W F1 mice.…”

“…Of note, the higher production of IFNα in response to CpG observed with some mouse strains was not a result of an intrinsic higher ability of pDC, rather it reflected the higher abundance of spleen pDCs in the mouse strain . We and others had recently found that pDCs from NZB/W F1 mice produce more IFNα in vitro as it confers a survival advantage, compared with those from C57BL/6 mice . However, it is unclear what the functional properties of parent strains are and what contribution of these properties is likely to confer autoimmunity in NZB/W F1 mice.…”