C-reactive protein directly suppresses Th1 cell differentiation and alleviates experimental autoimmune encephalomyelitis.
Human C-reactive protein (CRP) is a serum-soluble pattern recognition receptor that serves as a marker of inflammation and directly contributes to innate immunity. In this study, we show that human CRP also directly contributes to adaptive immunity, that is, native CRP binds specifically to human Jurkat T cells and to mouse naive CD4(+) T cells and modulates their Th1 and Th2 responses. In vitro both exogenously added (purified) and endogenously expressed (via transfection) human CRP inhibited Th1 differentiation and augmented Th2 differentiation of naive CD4(+) T cells. In vivo for human CRP transgenic compared with wild-type mice, a lesser proportion of the T cells recovered from the spleens of healthy animals were Th1 cells. Moreover, in both CRP transgenic mice and in wild-type mice treated with human CRP, during myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis both the Th1 cell response and disease severity were inhibited. These pattern recognition-independent actions of CRP directly on T cells highlights the potential for this soluble pattern recognition receptor to act as a tonic regulator of immunity, shaping global adaptive immune responses during both homeostasis and disease.
Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's Republic of China;
Lin
L
Zhang
Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's Republic of China;
Shan-Hui
SH
Liu
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294;
Tyler T
TT
Wright
Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's Republic of China;
Zhi-Yuan
ZY
Shen
Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's Republic of China;
Hai-Yun
HY
Li
Second Hospital of Lanzhou University, Lanzhou 730030, People's Republic of China;
Wei
W
Zhu
Department of Biopharmaceutical Sciences, Roosevelt University College of Pharmacy, Schaumburg, IL 60173; and.
Lawrence A
LA
Potempa
Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's Republic of China; wuy@lzu.edu.cn jsr@lzu.edu.cn alexszalai@uab.edu.
Shang-Rong
SR
Ji
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294; wuy@lzu.edu.cn jsr@lzu.edu.cn alexszalai@uab.edu.
Alexander J
AJ
Szalai
Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's Republic of China; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, People's Republic of China wuy@lzu.edu.cn jsr@lzu.edu.cn alexszalai@uab.edu.
Yi
http://orcid.org/0000-0003-0365-5590
Y
Wu
D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D011485:Protein Binding / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D063308:Myelin-Oligodendrocyte Glycoprotein; D002097:C-Reactive Protein