The transcription factor NR4A3 controls CD103+ dendritic cell migration

Park, Kiwon; Mikulski, Zbigniew; Seo, Goo-Young; Andreyev, Alexander Y.; Marcovecchio, Paola; Blatchley, Amy; Kronenberg, Mitchell; Hedrick, Catherine C.

doi:10.1172/jci87081

Cited by 31 publications

(41 citation statements)

References 63 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of NR4A3 on cDC migration is at least in part explained by the reduced expression of CCR7 on these cells (SI Appendix, Fig. S6 C and D), as previously reported (25). The normal distribution of cDCs in the skin of Nr4a3 −/− mice ( Fig.…”

Section: Nr4a3 Is Required For the In Vitro Differentiation Of Gm-csfsupporting

confidence: 82%

“…5K and SI Appendix, Fig. S6E), as well as in other peripheral tissues (25), further supports normal development of cDCs in the absence of NR4A3. In inflammatory conditions, Nr4a3 −/− splenic cDCs respond normally to LPS and Listeria by up-regulating the expression of CD86 and MHCII molecules (SI Appendix, Fig.…”

Section: Nr4a3 Is Required For the In Vitro Differentiation Of Gm-csfsupporting

confidence: 69%

“…5 I and J and SI Appendix, Fig. S6B), as reported by Park et al (25); note that the staining strategy used to identify the cDC1 and cDC2 subsets in Fig. 5H includes both resident and migratory DCs (SI Appendix, Fig.…”

Section: Nr4a3 Is Required For the In Vitro Differentiation Of Gm-csfmentioning

confidence: 65%

“…Mice lacking the expression of both NR4A1 and NR4A3 rapidly develop acute myeloid leukemia (22) and NR4A1, a close homolog of NR4A3, was shown to control the generation of the Ly6C lo monocyte subset and some macrophage functions (23,24). However, the specific role of NR4A3 in monocytes has not been investigated and only recently was a role attributed for NR4A3 in DC migration (25).…”

Section: Significancementioning

confidence: 99%

See 3 more Smart Citations

The orphan nuclear receptor NR4A3 controls the differentiation of monocyte-derived dendritic cells following microbial stimulation

Boulet

Daudelin

Odagiu

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In response to microbial stimulation, monocytes can differentiate into macrophages or monocyte-derived dendritic cells (MoDCs) but the molecular requirements guiding these possible fates are poorly understood. In addition, the physiological importance of MoDCs in the host cellular and immune responses to microbes remains elusive. Here, we demonstrate that the nuclear orphan receptor NR4A3 is required for the proper differentiation of MoDCs but not for other types of DCs. Indeed, the generation of DC-SIGN+ MoDCs in response to LPS was severely impaired in Nr4a3−/− mice, which resulted in the inability to mount optimal CD8+ T cell responses to gram-negative bacteria. Transcriptomic analyses revealed that NR4A3 is required to skew monocyte differentiation toward MoDCs, at the expense of macrophages, and allows the acquisition of migratory characteristics required for MoDC function. Altogether, our data identify that the NR4A3 transcription factor is required to guide the fate of monocytes toward MoDCs.

show abstract

Section: Nr4a3 Is Required For the In Vitro Differentiation Of Gm-csfsupporting

confidence: 82%

Section: Nr4a3 Is Required For the In Vitro Differentiation Of Gm-csfsupporting

confidence: 69%

Section: Nr4a3 Is Required For the In Vitro Differentiation Of Gm-csfmentioning

confidence: 65%

Section: Significancementioning

confidence: 99%

See 2 more Smart Citations

The orphan nuclear receptor NR4A3 controls the differentiation of monocyte-derived dendritic cells following microbial stimulation

Boulet

Daudelin

Odagiu

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…There are some transcription factors involved in DC migration, like IRF4, STAT-1, Runx2, and NR4A3 (14,(61)(62)(63). Zbtb46, a newly identified DC-specific transcriptional factor, has been suggested to regulate DC migration.…”

Section: B-arrestin 2 Deficiency In Dcs Aggravates Sle With DC Accumumentioning

confidence: 99%

Deficiency of β-Arrestin 2 in Dendritic Cells Contributes to Autoimmune Diseases

Cai

Yang

Yu³

et al. 2019

The Journal of Immunology

View full text Add to dashboard Cite

Altered migration and immune responses of dendritic cells (DCs) lead to inflammatory and autoimmune diseases. Our studies demonstrated that β-arrestin 2 deficiency promoted migration and cytokine production of mouse bone marrow–derived DCs. We further found that β-arrestin 2 directly interacted with Zbtb46, a DC-specific transcription factor. What’s more, our results suggested that the interaction between β-arrestin 2 and Zbtb46 might negatively regulate DC migration. Using RNA sequencing, we indicated that genes CD74, NR4A1, and ZFP36 might be the target genes regulated by the interaction between β-arrestin 2 and Zbtb46. Mice with selective deficiency of β-arrestin 2 in DCs developed severer experimental autoimmune encephalomyelitis with more DC infiltration in the CNS and increased IL-6 in serum. In the systemic lupus erythematosus mice model, Arrb2fl/fl Itgax-cre+ mice were prone to exacerbation of lupus nephritis with a higher level of IL-6 and DC accumulation. Taken together, our study identified β-arrestin 2 as a new regulator of DC migration and immune properties, providing new insights into the mechanisms underlying the development of autoimmune disease.

show abstract

Microenvironmental derived factors modulating dendritic cell function and vaccine efficacy: the effect of prostanoid receptor and nuclear receptor ligands

Raaijmakers

Ansems

2018

Cancer Immunol Immunother

View full text Add to dashboard Cite

Dendritic cells (DCs) are widely used in DC-based immunotherapies because of their capacity to steer immune responses. So far treatment success is limited and more functional knowledge on how DCs initiate and stably drive specific responses is needed. Many intrinsic and extrinsic factors contribute to how DCs skew the immune response towards immunity or tolerance. The origin and type of DC, its maturation status, but also factors they encounter in the in vitro or in vivo microenvironment they reside in during differentiation and maturation affect this balance. Treatment success of DC vaccines will, therefore, also depend on the presence of these factors during the process of vaccination. Identification and further knowledge of natural and pharmacological compounds that modulate DC differentiation and function towards a specific response may help to improve current DC-based immunotherapies. This review focuses on factors that could improve the efficacy of DC vaccines in (pre-)clinical studies to enhance DC-based immunotherapy, with a particular emphasis on compounds acting on prostanoid or nuclear receptor families.

show abstract

The transcription factor NR4A3 controls CD103+ dendritic cell migration

Cited by 31 publications

References 63 publications

The orphan nuclear receptor NR4A3 controls the differentiation of monocyte-derived dendritic cells following microbial stimulation

The orphan nuclear receptor NR4A3 controls the differentiation of monocyte-derived dendritic cells following microbial stimulation

Deficiency of β-Arrestin 2 in Dendritic Cells Contributes to Autoimmune Diseases

Microenvironmental derived factors modulating dendritic cell function and vaccine efficacy: the effect of prostanoid receptor and nuclear receptor ligands

Contact Info

Product

Resources

About