Syndecan-1-coating of interleukin-17-producing natural killer T cells provides a specific method for their visualization and analysis

Abstract

Natural killer T cells (NKT cells) are innate-like T cells that acquire effector functions while developing in the thymus, polarize into three distinct functional subsets viz. NKT1, NKT2 and NKT17 cells that produce interferon (IFN)-γ, interleukin (IL)-4 and IL-17, respectively. However, there has been no unique surface markers that define each subsets, forcing investigators to use intracellular staining of transcription factors and cytokines in combination of surface markers to distinguish among these subsets. Intracellular staining, however, causes apoptosis and prevents subsequent utilization of NKT cells in functional in vitro and in vivo assays that require viable cells. This limitation has significantly impeded understanding the specific properties of each subset and their interactions with each other. Therefore, there has been fervent efforts to find a specific markers for each NKT cell subset. We have recently identified that syndecan-1 (SDC-1; CD138) as a specific surface marker of NKT17 cells. This discovery now allows visualization of NKT17 in situ and study of their peripheral tissue distribution, characteristics of their TCR and viable sorting for in vitro and in vivo analysis. In addition, it lays the ground working for investigating significance of SDC-1 expression on this particular subset in regulating their roles in host defense and glucose metabolism.

Syndecan-1 Regulates Psoriasiform Dermatitis by Controlling Homeostasis of IL-17–Producing γδ T Cells

“…Recently, our group and subsequently others have identified sdc1 as a specific marker of IL-17-producing subset of NKT cells (NKT17) (11)(12)(13)(14)(15). We have also shown that sdc1 deficiency significantly increases frequency of NKT17 cells both in the thymus and periphery (11) and hence act as a negative regulator of NKT17 cell homeostasis (16).…”

“…Epithelia and other nonhematopoietic cells are the primary cell types that express sdc1 (8,9,16). We therefore determined whether sdc1 expressed on nonhematopoietic cells plays a role in regulating homeostasis of Tgd17 cells.…”

Disease Stage-Specific Pathogenicity of CD138 (Syndecan 1)-Expressing T Cells in Systemic Lupus Erythematosus

“…Syndecan 1 (CD138) is commonly used as a marker to identify plasmablasts and plasma cells (21). Recently, CD138 has been suggested to be a marker to distinguish IL-17 producing natural killer T17 (NKT17) cells from other invariant NKT cells based on its selective expression on NKT17 cells but not on NKT1 and NKT2 cells (22,23). Moreover, CD138+ T cells were observed accumulated in gut epithelia of aged C3H wild type as well as in the spleen and lymph nodes of FasL loss-of-function C3H gld mice (24).…”

Disease stage-specific pathogenicity of CD138 (syndecan 1)-expressing T cells in systemic lupus erythematosus

“…Syndecan 1 (CD138) is commonly used as a marker to identify plasmablasts and plasma cells [21]. Recently, CD138 has been suggested to be a a marker to distinguish IL-17 producing natural killer T17 (NKT17) cells from NKT1 cells, based on its selective expression on NKT17 cells but not on NKT1 cells [22, 23]. Moreover, CD138+ T cells were observed accumulated in gut epithelia of aged C3H wild type as well as in the spleen and lymph nodes of FasL loss-of-function C3H gld mice [24].…”