title: Nuclear receptor expression atlas in BMDCs: Nr4a2 restricts immunogenicity of BMDCs and impedes EAE.
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.
authors.affiliation: Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, 160036, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Saini
authors.affiliation: Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, 160036, India.|Department of Orthopedics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Sahil
authors.initials: S
authors.lastname: Mahajan
authors.affiliation: Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, 160036, India.
authors.forename: Pawan
authors.initials: P
authors.lastname: Gupta
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D055785:Gene Knockdown Techniques; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2
keywords: Dendritic cells ⋅ EAE ⋅ Immune tolerance ⋅ Nr4a2 ⋅ Nuclear receptors ⋅ Treg cells