IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis

Ruolan Liu; Ying Bai; Timothy L. Vollmer; Xue Feng Bai; Youngheun Jee; Yi yuan Tang; Denise I. Campagnolo; Mary Collins; Deborah A. Young; Antonio La Cava; Fu Dong Shi

doi:10.1016/j.expneurol.2007.11.004

IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis

Ruolan Liu, Ying Bai, Timothy L. Vollmer, Xue Feng Bai, Youngheun Jee, Yi yuan Tang, Denise I. Campagnolo, Mary Collins, Deborah A. Young, Antonio La Cava, Fu Dong Shi

Psychological Sciences

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

The IL-21 receptor (IL-21R) consists of a unique subunit and a common γ chain (γ_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.

Original language	English
Pages (from-to)	14-24
Number of pages	11
Journal	Experimental Neurology
Volume	211
Issue number	1
DOIs	https://doi.org/10.1016/j.expneurol.2007.11.004
State	Published - May 2008

Keywords

Autoimmunity
CD4CD25 regulatory T cells
EAE
IL-21 receptor
NK cells

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10.1016/j.expneurol.2007.11.004

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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 γ chain (γc) 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.",

keywords = "Autoimmunity, CD4CD25 regulatory T cells, EAE, IL-21 receptor, NK cells",

author = "Ruolan Liu and Ying Bai and Vollmer, {Timothy L.} and Bai, {Xue Feng} and Youngheun Jee and Tang, {Yi yuan} and Campagnolo, {Denise I.} and Mary Collins and Young, {Deborah A.} and {La Cava}, Antonio and Shi, {Fu Dong}",

note = "Funding Information: We thank W. Piao and S. Rhodes for their technical support, P. Minick for editorial assistance. This work was supported by grants from the NMSS (National Multiple Sclerosis Society, FDS), from the MDA (Muscular Dystrophy Association, FDS), Barrow Neurological Foundation (FDS and TLV) and the National Institutes of Health (ALC, DIC). Ruolan Liu is a recipient of a development grant from the MDA. ",

year = "2008",

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doi = "10.1016/j.expneurol.2007.11.004",

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AU - Liu, Ruolan

AU - Bai, Ying

AU - Vollmer, Timothy L.

AU - Bai, Xue Feng

AU - Jee, Youngheun

AU - Tang, Yi yuan

AU - Campagnolo, Denise I.

AU - Collins, Mary

AU - Young, Deborah A.

AU - La Cava, Antonio

AU - Shi, Fu Dong

N1 - Funding Information: We thank W. Piao and S. Rhodes for their technical support, P. Minick for editorial assistance. This work was supported by grants from the NMSS (National Multiple Sclerosis Society, FDS), from the MDA (Muscular Dystrophy Association, FDS), Barrow Neurological Foundation (FDS and TLV) and the National Institutes of Health (ALC, DIC). Ruolan Liu is a recipient of a development grant from the MDA.

PY - 2008/5

Y1 - 2008/5

N2 - The IL-21 receptor (IL-21R) consists of a unique subunit and a common γ chain (γc) 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.

AB - The IL-21 receptor (IL-21R) consists of a unique subunit and a common γ chain (γc) 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.

KW - Autoimmunity

KW - CD4CD25 regulatory T cells

KW - EAE

KW - IL-21 receptor

KW - NK cells

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SP - 14

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JO - Experimental Neurology

JF - Experimental Neurology

IS - 1

ER -

IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis

Abstract

Keywords

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