title: IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis.
abstract: The IL-21 receptor (IL-21R) consists of a unique subunit and a common gamma chain (gamma(c)) that is shared with other cytokines including IL-2, IL-4, IL-7, and IL-15. The interaction between IL-21 and IL-21R results in significant effects on both innate and adaptive immune responses. In this study we examined the influence of IL-21R deficiency (IL-21R(-/-)) on the development of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). IL-21R(-/-) mice developed EAE earlier and more severe neurological impairment than control mice, yet those mice could effectively recover from neurological deficits. The impact on EAE initiation by IL-21R deficiency was associated with a defect of CD4(+)CD25(+) T regulatory (Treg) cells and a down-regulated expression of Foxp3. The recovery from IL-21R(-/-) EAE was correlated with an expansion of Treg cells as well as an organ-specific redistribution of NK cells. These results suggest that a temporal influence of IL-21 on the activity of immunoregulatory circuits can be important in the modulation of the course of the autoimmune disease.
authors: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013, USA.
authors: Ruolan
authors: R
authors: Liu
authors: Ying
authors: Y
authors: Bai
authors: Timothy L
authors: TL
authors: Vollmer
authors: Xue-Feng
authors: XF
authors: Bai
authors: Youngheun
authors: Y
authors: Jee
authors: Yi-yuan
authors: YY
authors: Tang
authors: Denise I
authors: DI
authors: Campagnolo
authors: Mary
authors: M
authors: Collins
authors: Deborah A
authors: DA
authors: Young
authors: Antonio
authors: A
authors: La Cava
authors: Fu-Dong
authors: FD
authors: Shi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D049109:Cell Proliferation; D003711:Demyelinating Diseases / Q000209:etiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology*; D006023:Glycoproteins; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010446:Peptide Fragments; D053655:Receptors, Interleukin-21 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D006023:Glycoproteins; D007376:Interleukin-2; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D063308:Myelin-Oligodendrocyte Glycoprotein; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010446:Peptide Fragments; D053655:Receptors, Interleukin-21; C445081:myelin oligodendrocyte glycoprotein (35-55)