Chi Hongbo and other teams have written 6 Nature/Cell/NCB articles in 1 year, and have made important progress in the field of immunization

iNature

Phosphatase and tensin homologue (PTEN) is a frequently mutated tumor suppressor gene that plays an important role
in T cell biology.
Mice carrying PTEN-deficient T cells form T-cell lymphoma and have defects
in immune tolerance and β selection of traditional T cells.
In addition, the loss of PTEN heterozygotes leads to the development of late-onset lymphoproliferative syndrome, triggering a fatal autoimmune response
through an unknown mechanism.
In humans, germline mutations in the PTEN gene are associated with several medical conditions, collectively known as PTEN hamartoma tumour syndrome (PHTS), which are associated with an increased risk of tumorigenesis and the development of autoimmunity and lymphoid hyperplasia, although little is known about its underlying pathogenic mechanisms
.

On October 27, 2022, Chi Hongbo and Yang Kai of St.
Jude Children's Research Hospital jointly published a joint newsletter entitled "PTEN directs developmental and metabolic signaling for innate-like T cell fate and tissue" online in Nature Cell Biology Homeostasis", which found that PTEN coordinates a two-step developmental process
between antigen receptors and the IL-23-Stat3 signaling pathway and the production of type 17 innate T cells.
The loss of PTEN leads to a marked accumulation
of mature congenital T cells that produce IL-17 in the thymus.
IL-23 is critical for their accumulation, and the absence of IL-23 or IL-17 signals can correct the decreased
survival of female PTEN haplo-deficient mice in human patient models with PTEN mutations.

Single-cell transcriptome and network analysis revealed the dynamic regulation
of PTEN, mTOR, and metabolic activity accompanying cell programming with type 17 cell programming.
In addition, deletion of mTORC1 or mTORC2 blocks PTEN loss-driven cell accumulation in type 17 cells, which is further affected
by the Foxo1 and Stat3 pathways.
In conclusion, the study establishes developmental and metabolic signaling networks that support fate-determination of type 17 cells and their functional effects
that coordinate PTEN-dependent tissue homeostasis.

In addition, on June 22, 2022, Douglas R.
Green and Chi Hongbo of St.
Jude Children's Research Hospital published a joint newsletter entitled "cBAF complex components and MYC cooperate early inCD8⁺" online in Nature Tcell fate", which identified multiple components
of the mammalian classical BRG1/BRM associated factor (cBAF) using a CRISPR-based screening of negative regulators of Tmem cell production in vivo.
Several components of the cBAF complex are critical for the differentiation of activated CD8⁺ T cells into T effector (T _eff) cells, and their absence promotes T _{mem in vivo} Formation
of cells.
During the first division of activated CD8⁺ T cells, cBAF and MYC often co-mate
asymmetrically with the two daughter cells.
Daughter cells with high MYC and high cBAF showed cell fate trajectories towards T eff cells, while daughter cells with low MYC and low cBAF preferentially differentiated towards T _mem cells
。 The cBAF complex and MYC physically interact to establish chromatin landscapes
in activated CD8+ T cells.
Treatment of naïve CD8⁺ T cells with putative cBAF inhibitors significantly improved efficacy in mouse solid tumor models prior to the generation of chimeric antigen receptor T (CAR-T) cells, during the first 48 hours of activation.

Taken together, the findings establish cBAF as a negative determinant of T_mem cell fate and suggest that manipulating cBAF early in T cell differentiation can improve cancer immunotherapy (click to read).

On November 18, 2021, the Chi Hongbo team at St.
Jude Children's Research Hospital published a paper titled "CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity" online in Nature ", which uses genome-wide CRISPR screening binding protein-protein interaction networks to identify regulatory modules that mediate immune receptor and nutrition-dependent signaling to mTORC1
in mouse regulatory T (Treg) cells.
The results establish epigenetic and post-translational mechanisms that support how nutrient transporters and sensors interact with immune signals for tertiary regulation of mTORC1 activity and determine their key role in licensing T cell immunity and immune tolerance (click to read).

On July 7, 2021, the Chi Hongbo team of St.
Jude Children's Research Hospital in the United States published a paper entitled "Metabolic control ofT_FHcells and humoral" in Nature immunity by phosphatidylethanolamine", which showed that the cytidine diphosphate (CDP)-ethanolamine pathway coordinates CXCR5 expression and localization in response to T_FH cells and humoral immunity
。 Using CRISPR-Cas9 screening and functional validation in mice, the study identified ETNK1, PCYT2, and SELENOI as selective post-transcriptional regulators of T_FH cell differentiation to function
by promoting surface expression and functional role of CXCR5.
T_FH cells exhibit a unique lipid metabolism program, with PE distributed in the outer layer of the plasma membrane, colocalized
with CXCR5.
De novo synthesis of PE via the CDP-ethanolamine pathway coordinates these events to prevent internalization and degradation
of CXCR5.
Gene deletion of Pcyt2 instead of Pcyt1a (mediating the CDP-choline pathway) in activated T cells impairs T_FH cell differentiation, which is associated with
a reduced humoral immune response.
The surface level of PE and CXCR5 expression on B cells also depends on Pcyt2
.
In conclusion, the results suggest that phospholipid metabolism coordinates the post-transcriptional mechanisms of T_FH cell differentiation and humoral immunity, highlighting the metabolic control
of environment-dependent immune signaling and effector programs.

On February 25, 2021, the Chi Hongbo team at St.
Jude Children's Research Hospital in the United States published a paper entitled "In vivo CRISPR screening reveals nutrient signaling processes underpinningCD8" online at Cell + T cell fate decisions The research paper, which designed an in vivo screening system based on CRISPR/Cas9, reveals key cellular metabolic pathways that regulate the fate decisions of CD8⁺ T cells (click to read).

。

On February 24, 2021, the Chi Hongbo team of St.
Jude Children's Research Hospital in the United States published a paper entitled "Lipid signalling enforces functional specialization of Tregcells in tumours" in Nature ", which demonstrates that inhibition of lipid synthesis and metabolic signaling dependent on sterol regulatory element-binding proteins (SREBPs) in Treg cells releases an effective anti-tumor immune response without autoimmune toxicity
.
Together, the study suggests that metabolic reprogramming enhances the functional specificity of Treg cells in tumors, providing new avenues for targeting these cells for cancer treatment (click to read).