Suppression of expression and function of negative immune regulator PD-1 by certain pattern recognition and cytokine receptor signals associated with immune system danger

International Immunology
Xuemei ZhongThomas L Rothstein

Abstract

Stimulation of certain cytokine and pattern recognition receptors enhances adaptive immune responses, and in chronic situations, may play a role in the loss of self-tolerance. We hypothesized that in addition to upregulating positive immune receptors (i.e. co-stimulatory molecules), certain cytokine and pattern recognition signals might downregulate negative immune receptors, removing a potential barrier to lymphocyte responsiveness. The newly identified CD28 family member Programmed Death-1 (PD-1) is an inhibitory receptor involved in peripheral tolerance, as evidenced by the frank autoimmunity and autoantibody formation found in PD-1-deficient mice. Here we report that antigen-receptor induced PD-1 expression on murine B cells is markedly reduced by certain signals associated with immune system danger, including LPS, CpG oligodeoxynucleotides and several pro-inflammatory cytokines, through distinct signaling pathways. We further report for the first time that engagement of PD-1 inhibits cell cycle progression in primary B cells and that modulation of PD-1 expression by CpG or IL-4 significantly reverses such inhibition. Our data suggest a novel mechanism for enhancement of normal immune responses and disruption of normal tole...Continue Reading

Citations

Oct 30, 2008·Journal of Immunotoxicology·Russell L Dedrick
Oct 18, 2005·Autoimmunity·Taku Okazaki, Jian Wang
Jan 3, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Hanlu DingWenda Gao
May 12, 2005·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Hanlu DingWenda Gao
Sep 16, 2009·Immunology Letters·Raymond M WongAdrian I Bot
May 19, 2016·Immunity·Frank A SchildbergArlene H Sharpe
Mar 13, 2017·Journal of Neuroimmunology·Edyta Pawlak-AdamskaMalgorzata Bilinska
Dec 28, 2019·Cancers·Sarah L PicardoAaron R Hansen
Oct 18, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karen M Haas
Jan 28, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jerome T McKayKaren M Haas
Jan 13, 2021·Cancers·Marc ArmengolGaël Roué

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

B cell Tolerance

B cell tolerance is maintained through mechanisms that can reversibly or irreversibly silence autoreactive B lymphocytes. Here is the latest research.