scholarly journals DOCK8-expressing T follicular helper cells newly generated beyond self-organized criticality cause systemic lupus erythematosus

iScience ◽  
2021 ◽  
pp. 103537
Author(s):  
Shunichi Shiozawa ◽  
Ken Tsumiyama ◽  
Yumi Miyazaki ◽  
Kenichi Uto ◽  
Keiichi Sakurai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
T Follicular Helper Cells ◽  
Systemic Lupus ◽  
Helper Cells ◽  
Self Organized ◽  
Follicular Helper ◽  
Self Organized Criticality

scholarly journals T follicular helper cells, interleukin-21 and systemic lupus erythematosus

Rheumatology ◽  
2016 ◽  
pp. kew297 ◽  
Author(s):  
Noémie Gensous ◽  
Nathalie Schmitt ◽  
Christophe Richez ◽  
Hideki Ueno ◽  
Patrick Blanco
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
T Follicular Helper Cells ◽  
Systemic Lupus ◽  
Helper Cells ◽  
Follicular Helper ◽  
Interleukin 21

scholarly journals T Follicular Helper Cells and Regulatory B Cells Dynamics in Systemic Lupus Erythematosus

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88441 ◽  
Author(s):  
Xue Yang ◽  
Ji Yang ◽  
Yiwei Chu ◽  
Yu Xue ◽  
Dandan Xuan ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Regulatory B Cells ◽  
T Follicular Helper Cells ◽  
Systemic Lupus ◽  
Helper Cells ◽  
Follicular Helper

Newly Generated DOCK8-Expressing T Follicular Helper Cells Cause Systemic Lupus Erythematosus

2021 ◽  
Author(s):  
Shunichi Shiozawa ◽  
Ken Tsumiyama ◽  
Yumi Miyazaki ◽  
Kenichi Uto ◽  
Keiichi Sakurai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
T Follicular Helper Cells ◽  
Systemic Lupus ◽  
Helper Cells ◽  
Follicular Helper

scholarly journals A Newly Generated DOCK8-expressing T Follicular Helper Cell Type, aiCD4 T Cell, Causes Systemic Lupus Erythematosus: Self-Organized Criticality Theory

2020 ◽  
Author(s):  
Shunichi Shiozawa ◽  
Ken Tsumiyama ◽  
Keiichi Sakurai ◽  
Takahiko Horiuchi ◽  
Tsukasa Matsubara ◽  
...  
Keyword(s):  
T Cells ◽  
Lupus Erythematosus ◽  
Cd4 T Cells ◽  
Cell Type ◽  
Systemic Lupus ◽  
Self Organized ◽  
Follicular Helper ◽  
Helper Cell Type ◽  
Self Organized Criticality ◽  
T Follicular Helper Cell

Abstract Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease of unknown cause. We show here that a novel T follicular helper cell type expressing the guanine nucleotide exchange factor DOCK8 on the cell surface causes SLE. These cells, which we have designated autoantibody-inducing CD4 T (aiCD4 T) cells, are generated after resuscitation from anergy following strong TCR stimulation by antigen. When mice normally not prone to autoimmune disease were repeatedly immunized with an antigen such as OVA, they generated DOCK8+ CD4 T cells. These DOCK8+ CD4 T cells, in vivo and also upon transfer to naïve mice, induced a variety of autoantibodies and lesions characteristic of SLE. TCR repertoire analyses showed that a substantial number of novel TCR repertoires were generated in the DOCK8+ CD4 T cells, which induced novel autoantibodies upon transfer to naïve mice. DOCK8+ CD4 T cells are localized in splenic red pulp, the space immunoreactive against a variety of antigens, and specifically increased in the peripheral blood of SLE patients in association with disease activity. Anti-DOCK8 antibody treatment ameliorated the lesions induced by DOCK8+ CD4 T cells and in lupus model (NZB x W) F1 mice. Thus, when CD4 T cells are overstimulated by an external disturbance, i.e., repeatedly stimulated with antigen, to levels that surpass the system’s self-organized criticality, these cells express DOCK8 on the cell surface and acquire autoreactivity via TCR re-revision at the periphery. These DOCK8+ CD4 T cells subsequently induce a variety of autoantibodies and SLE.

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