The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
LAG-3 Regulates Plasmacytoid Dendritic Cell Homeostasis
Open accessAbstract
Lymphocyte activation gene 3 (LAG-3) is a CD4-related, activation-induced cell surface molecule expressed by various lymphoid cell types and binds to MHC class II with high affinity. We have previously shown that LAG-3 negatively regulates the expansion of activated T cells and T cell homeostasis, and is required for maximal regulatory T cell function. In this study, we demonstrate for the first time that LAG-3 is also expressed on CD11clow/B220+/PDCA-1+ plasmacytoid dendritic cells (pDCs). Lag3 expression, as determined by real time PCR, was ∼10-fold greater in pDCs than in either regulatory T cells or activated T effector cells. Activated pDCs also generate ∼5 times more sLAG-3 than activated T cells. LAG-3-deficient pDCs proliferate and expand more than wild-type pDCs in vivo in response to the TLR9 ligand, CpG. However, the effect of LAG-3 appears to be selective as there was no effect of LAG-3 on the expression of MHC class II, TLR9, and chemokine receptors, or on cytokine production. Lastly, adoptive transfer of either Lag3+/+ or Lag3−/− T cells plus or minus Lag3+/+ or Lag3−/− pDCs defined a role for LAG-3 in controlling pDC homeostasis as well as highlighting the consequences of deregulated Lag3−/− pDCs on T cell homeostasis. This raised the possibility of homeostatic reciprocity between T cells and pDCs. Collectively, our data suggests that LAG-3 plays an important but selective cell intrinsic and cell extrinsic role in pDC biology, and may serve as a key functional marker for their study.
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Self-citationMouse type I IFN-producing cells are immature APCs with plasmacytoid morphology
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Metadata
- Authors
- Workman, C. J., Wang, Y., El Kasmi, K. C., Pardoll, D. M., Murray, P. J., Drake, C. G., & Vignali, D. A. A.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-02
- Volume
- 182
- Issue
- 4
- Pages
- 1885-1891
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2169212859
- Cited by
- 316
- References
- 36
- FWCI
- 11.46
- Type
- journal article
- Language
- en
- Open access
- green
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