Nuclear receptor expression atlas in BMDCs: Nr4a2 restricts immunogenicity of BMDCs and impedes EAE. Issue 8 (8th June 2016)

• Record Type: Journal Article
• Authors: Saini, Ankita; Mahajan, Sahil; Gupta, Pawan
• Is Part Of: European journal of immunology. Volume 46:Issue 8(2016)
• Page Start: 1842
• Page End: 1853
• Publication Date: 2016-06-08
• Subjects: Dendritic cells ⋅ EAE ⋅ Immune tolerance ⋅ Nr4a2 ⋅ Nuclear receptors ⋅ Treg cells; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201546229
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : This study identifies 39 nuclear receptors being expressed in bone marrow derived dendritic cells. Of these, Nr4a2 limits the immunogenicity while endowing DCs with tolerogenic potential(I) . In vivo administration of such bone marrow derived dendritic cells, which have ectopically expressing Nr4a2, attenuates EAE(II) . Abstract : The nuclear receptor (NR) superfamily of transcription factors regulates various key aspects of physiological processes; however, their role(s) in immune cells' function are just beginning to unravel. Although few NRs have been shown to be critical for dendritic cell (DC) function, a lack of knowledge about their complete representation in DCs has limited the ability to harness their full potential. Here, we performed a comprehensive NR expression profiling and identified the key members of NR superfamily being expressed in immature, immunogenic, and tolerogenic DCs. Comparative analysis revealed discrete changes in the expression of various NRs among the studied DC subtypes, indicating a likely role in the modulation of DC functionality. Next, we characterized Nr4a2, a member of orphan NR family, and found that it suppresses the activation of bone marrow derived dendritic cells triggered by LPS. Overexpression and knockdown of Nr4a2 demonstrated that Nr4a2 orchestrates the expression of immunoregulatory genes, hence inducing a tolerogenic phenotype in bone marrow derived dendritic cells. Furthermore, we also found that Nr4a2 provides protection from EAE by promoting an increase in Treg cells, while limiting effector T cells. Our findings suggest a previously unidentified role for Nr4a2 as a regulator of DC tolerogenicity and demonstrate its potential as therapeutic target in DC‐associated pathophysiologies.