scholarly journals MiR-23~27~24–mediated control of humoral immunity reveals a TOX-driven regulatory circuit in follicular helper T cell differentiation

2019 ◽  
Vol 5 (12) ◽  
pp. eaaw1715 ◽  
Author(s):  
Cheng-Jang Wu ◽  
Sunglim Cho ◽  
Hsi-Yuan Huang ◽  
Chun-Hao Lu ◽  
Jasmin Russ ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Humoral Immunity ◽  
Cell Biology ◽  
Dependent Manner ◽  
Cell Responses ◽  
Follicular Helper ◽  
Regulatory Circuit ◽  
Follicular Helper T Cell ◽  
Immune Challenges ◽  
And Function

Follicular helper T (TFH) cells are essential for generating protective humoral immunity. To date, microRNAs (miRNAs) have emerged as important players in regulating TFH cell biology. Here, we show that loss of miR-23~27~24 clusters in T cells resulted in elevated TFH cell frequencies upon different immune challenges, whereas overexpression of this miRNA family led to reduced TFH cell responses. Mechanistically, miR-23~27~24 clusters coordinately control TFH cells through targeting a network of genes that are crucial for TFH cell biology. Among them, thymocyte selection–associated HMG-box protein (TOX) was identified as a central transcription regulator in TFH cell development. TOX is highly up-regulated in both mouse and human TFH cells in a BCL6-dependent manner. In turn, TOX promotes the expression of multiple molecules that play critical roles in TFH cell differentiation and function. Collectively, our results establish a key miRNA regulon that maintains optimal TFH cell responses for resultant humoral immunity.

scholarly journals CTLA-4 controls follicular helper T-cell differentiation by regulating the strength of CD28 engagement

2014 ◽  
Vol 112 (2) ◽  
pp. 524-529 ◽  
Author(s):  
Chun Jing Wang ◽  
Frank Heuts ◽  
Vitalijs Ovcinnikovs ◽  
Lukasz Wardzinski ◽  
Chantelle Bowers ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Responses ◽  
Dependent Manner ◽  
Cell Responses ◽  
Follicular Helper ◽  
Follicular Helper T Cell

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an essential regulator of T-cell responses, and its absence precipitates lethal T-cell hyperactivity. However, whether CTLA-4 acts simply to veto the activation of certain clones or plays a more nuanced role in shaping the quality of T-cell responses is not clear. Here we report that T cells in CTLA-4–deficient mice show spontaneous T-follicular helper (TFH) differentiation in vivo, and this is accompanied by the appearance of large germinal centers (GCs). Remarkably, short-term blockade with anti–CTLA-4 antibody in wild-type mice is sufficient to elicit TFH generation and GC development. The latter occurs in a CD28-dependent manner, consistent with the known role of CTLA-4 in regulating the CD28 pathway. CTLA-4 can act by down-regulating CD80 and CD86 on antigen presenting cells (APCs), thereby altering the level of CD28 engagement. To mimic reduced CD28 ligation, we used mice heterozygous for CD28, revealing that the magnitude of CD28 engagement is tightly linked to the propensity for TFH differentiation. In contrast, other parameters of T-cell activation, including CD62L down-regulation and Ki67 expression, were relatively insensitive to altered CD28 level. Altered TFH generation as a result of graded reduction in CD28 was associated with decreased numbers of GC B cells and a reduction in overall GC size. These data support a model in which CTLA-4 control of immunity goes beyond vetoing T-cell priming and encompasses the regulation of TFH differentiation by graded control of CD28 engagement.

scholarly journals IκBNS enhances follicular helper T-cell differentiation and function downstream of ASCl2

2017 ◽  
Vol 140 (1) ◽  
pp. 288-291.e8 ◽  
Author(s):  
Junichi Hosokawa ◽  
Kotaro Suzuki ◽  
Kazuyuki Meguro ◽  
Shigeru Tanaka ◽  
Yuko Maezawa ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Helper T Cell ◽  
Follicular Helper ◽  
Follicular Helper T Cell ◽  
And Function

scholarly journals Follicular Helper T Cell Differentiation Requires Continuous Antigen Presentation that Is Independent of Unique B Cell Signaling

Immunity ◽  
2010 ◽  
Vol 33 (2) ◽  
pp. 241-253 ◽  
Author(s):  
Elissa K. Deenick ◽  
Anna Chan ◽  
Cindy S. Ma ◽  
Dominique Gatto ◽  
Pamela L. Schwartzberg ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Cell Signaling ◽  
B Cell ◽  
Antigen Presentation ◽  
T Cell Differentiation ◽  
Helper T Cell ◽  
B Cell Signaling ◽  
Follicular Helper ◽  
Follicular Helper T Cell

scholarly journals Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Sungjun Park ◽  
Seungwon Lee ◽  
Choong-Gu Lee ◽  
Guk Yeol Park ◽  
Hyebeen Hong ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Helper T Cell ◽  
Follicular Helper ◽  
Follicular Helper T Cell

scholarly journals Roquin Paralogs 1 and 2 Redundantly Repress the Icos and Ox40 Costimulator mRNAs and Control Follicular Helper T Cell Differentiation

Immunity ◽  
2013 ◽  
Vol 38 (4) ◽  
pp. 655-668 ◽  
Author(s):  
Katharina U. Vogel ◽  
Stephanie L. Edelmann ◽  
Katharina M. Jeltsch ◽  
Arianna Bertossi ◽  
Klaus Heger ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Helper T Cell ◽  
Follicular Helper ◽  
Follicular Helper T Cell ◽  
And Control

scholarly journals Prolonged follicular helper T cell responses in ME7 scrapie-infected mice

Prion ◽  
2018 ◽  
Vol 12 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Soochan Kim ◽  
Sinsuk Han ◽  
Taehyun Kim ◽  
Jeehoon Nam ◽  
Yong-Sun Kim ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Helper T Cell ◽  
Cell Responses ◽  
Follicular Helper ◽  
Follicular Helper T Cell

scholarly journals mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation

Immunity ◽  
2016 ◽  
Vol 45 (3) ◽  
pp. 540-554 ◽  
Author(s):  
Hu Zeng ◽  
Sivan Cohen ◽  
Cliff Guy ◽  
Sharad Shrestha ◽  
Geoffrey Neale ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Glucose Metabolism ◽  
T Cell Differentiation ◽  
Kinase Signaling ◽  
Helper T Cell ◽  
Follicular Helper ◽  
Follicular Helper T Cell
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