title: Hormonal Modulation of Dendritic Cells Differentiation, Maturation and Function: Implications for the Initiation and Progress of Systemic Autoimmunity.
abstract: Hormonal homeostasis is crucial for keeping a competent and healthy immune function. Several hormones can modulate the function of various immune cells such as dendritic cells (DCs) by influencing the initiation of the immune response and the maintenance of peripheral tolerance to self-antigens. Hormones, such as estrogens, prolactin, progesterone and glucocorticoids may profoundly affect DCs differentiation, maturation and function leading to either a pro-inflammatory or an anti-inflammatory (or tolerogenic) phenotype. If not properly regulated, these processes can contribute to the pathogenesis of autoimmune disease. An unbalanced hormonal status may affect the production of pro-inflammatory cytokines, the expression of activating/inhibitory receptors and co-stimulatory molecules on conventional and plasmacytoid DCs (pDCs), conferring susceptibility to develop autoimmunity. Estrogen receptor (ER)-α signaling in conventional DCs can promote IFN-α and IL-6 production and induce the expression of CD40, CD86 and MHCII molecules. Furthermore, estrogen modulates the pDCs response to Toll-like receptor ligands enhancing T cell priming. During lupus pathogenesis, ER-α deficiency decreased the expression of MHC II on pDCs from the spleen. In contrast, estradiol administration to lupus-prone female mice increased the expression of co-stimulatory molecules, enhanced the immunogenicity and produced large amounts of IL-6, IL-12 and TNF-α by bone marrow-derived DCs. These data suggest that estradiol/ER signaling may play an active role during lupus pathology. Similarly, understanding hormonal modulation of DCs may favor the design of new therapeutic strategies based on autologous tolerogenic DCs transfer, especially in sex-biased systemic autoimmune diseases. In this review, we discuss recent data relative to the role of different hormones (estrogen, prolactin, progesterone and glucocorticoids) in DC function during systemic autoimmune pathogenesis.
authors: Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET, Mendoza, Argentina. jpmackern@mendoza-conicet.gob.ar.|Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina. jpmackern@mendoza-conicet.gob.ar.|Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Millennium Institute of Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile. jpmackern@mendoza-conicet.gob.ar.
authors: Juan Pablo
authors: JP
authors: Mackern-Oberti
authors: Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Millennium Institute of Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Evelyn L
authors: EL
authors: Jara
authors: Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas y Facultad de Medicina, Millennium Institute of Immunology and Immunotherapy, Universidad Andrés Bello, Santiago, Chile.
authors: Claudia A
authors: CA
authors: Riedel
authors: Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Millennium Institute of Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile. akalergis@bio.puc.cl.|Departamento de Endocrinología, Facultad de Medicina, Millennium Institute of Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile. akalergis@bio.puc.cl.|INSERM U1064, Nantes, France. akalergis@bio.puc.cl.
authors: Alexis M
authors: AM
authors: Kalergis
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy*; D053264:B-Cell Activating Factor / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology*; D004195:Disease Models, Animal; D004967:Estrogens / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000378:metabolism; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D011374:Progesterone / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D004967:Estrogens; D005938:Glucocorticoids; D006728:Hormones; D017452:Receptors, IgG; C505719:TNFSF13B protein, human; D051193:Toll-Like Receptors; D011374:Progesterone; D011388:Prolactin
keywords: Autoimmunity; Dendritic cells; Estrogen; Glucocorticoids; Progesterone; Prolactin; Systemic lupus erythematosus