IL-21 and IL-21 Receptor Expression in Lymphocytes and Neurons in Multiple Sclerosis Brain

• Published in: The American journal of pathology Vol. 178; no. 2; pp. 794 - 802
• Main Authors: Tzartos, John S, Craner, Matthew J, Friese, Manuel A, Jakobsen, Karen B, Newcombe, Jia, Esiri, Margaret M, Fugger, Lars
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.02.2011; American Society for Investigative Pathology
• Subjects: Acute Disease; Antigens, CD19 - metabolism; B-Lymphocytes - metabolism; Biological and medical sciences; Brain - metabolism; Brain - pathology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - metabolism; Chronic Disease; Humans; Interleukin-21 Receptor alpha Subunit - genetics; Interleukin-21 Receptor alpha Subunit - metabolism; Interleukins - genetics; Interleukins - metabolism; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Multiple Sclerosis - immunology; Multiple Sclerosis - metabolism; Multiple Sclerosis - pathology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Neurons - metabolism; Neurons - pathology; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Regular; RNA, Messenger - genetics; RNA, Messenger - metabolism; Up-Regulation - genetics; Nervous system diseases; Anatomic pathology; Multiple sclerosis; Neuron; Central nervous system disease; Central nervous system; Interleukin 21; Lymphocyte; Inflammatory disease; Encephalon; Biological receptor
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2010.10.043

IL-17–producing CD4+ T cells (Th-17) contribute to the pathogenesis of experimental autoimmune encephalomyelitis and are associated with active disease in multiple sclerosis (MS). In addition to IL-17, Th-17 cells can also express IL-21, IL-22, and IL-6 under Th-17–polarizing conditions (IL-6 and transforming growth factor-β). In this study we investigated IL-21 and IL-21 receptor (IL-21R) expression in MS lesions by in situ hybridization and immunohistochemistry. We detected strongly IL-21+ infiltrating cells predominantly in acute but also in chronic active white matter MS lesions in which IL-21 expression was restricted to CD4+ cells. In contrast, IL-21R was much more broadly distributed on CD4+ , CD19+ , and CD8+ lymphocytes but not major histocompatibility complex class-II+ macrophages/microglia. Interestingly, in cortical areas we detected both IL-21 and IL-21R expression by neurons. These findings suggest role(s) for IL-21 in both the acute and chronic stages of MS via direct effects on T and B lymphocytes and, demonstrated for the first time, also on neurons.