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Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire

Lo and colleagues report that double-positive thymocytes from neonates express less Zap70 and show reduced Ca^2⁺/NFAT signaling compared to double-positive thymocytes from older thymi. This diminished Ca^2⁺ signaling alters negative selection for self-reactive TCRs, resulting in a cell-intrinsic temporal window for regulatory T versus conventional T cell development in the thymus.

Brian D. Stadinski
Elizabeth A. Mills
Wan-Lin Lo
ResearchOpen Access07 Oct 2025
Nature Immunology

P: 1-14
Aberrant T follicular helper cells generated by T_H17 cell plasticity in the gut promote extraintestinal autoimmunity

Wu and colleagues show that T_H17 cells arising in the gut in response to segmented filamentous bacteria can convert to highly mobile follicular helper T_FH17 cells, emigrate to the spleen and regulate auto-antibody production and arthritis severity.

Tingting Fan
Chi Tai
Hsin-Jung Joyce Wu
Research30 Apr 2025
Nature Immunology

Volume: 26, P: 790-804
A single-amino acid substitution in the adaptor LAT accelerates TCR proofreading kinetics and alters T-cell selection, maintenance and function

Lo and colleagues provide evidence for the TCR kinetic proofreading model by LAT Gly135Asp alteration to reveal functional consequences of altered kinetics in TCR activation in thymic selection and mature T-cell responses.

Wan-Lin Lo
Miriam Kuhlmann
Arthur Weiss
ResearchOpen Access13 Mar 2023
Nature Immunology

Volume: 24, P: 676-689
Intrinsic CD4⁺ T cell sensitivity and response to a pathogen are set and sustained by avidity for thymic and peripheral complexes of self peptide and MHC

Interactions of the TCR with self peptide–MHC are crucial to T cell development. Allen and colleagues show that the strength of such interactions also determines the intrinsic T cell functionality and responses to pathogens.

Stephen P Persaud
Chelsea R Parker
Paul M Allen
Research02 Feb 2014
Nature Immunology

Volume: 15, P: 266-274
An endogenous peptide positively selects and augments the activation and survival of peripheral CD4⁺ T cells

Endogenous peptides that positively select major histocompatibility complex class II-restricted T cell receptors have not yet been identified. Groups led by Davis and Allen identify several such peptides and find that they influence activation and homeostasis of peripheral T cells.

Wan-Lin Lo
Nathan J Felix
Paul M Allen
Research04 Oct 2009
Nature Immunology

Volume: 10, P: 1155-1161
Two CTLA-4 ligands, separate pHates

The inhibitory checkpoint molecule CTLA-4 is essential for regulatory T cell function. A new study highlights the differential manner in which CTLA-4 binds CD80 and CD86, which determines its cellular fate and orchestrates immune tolerance regulation.

Preston A. Humphries
Wan-Lin Lo
News & Views23 Aug 2022
Nature Immunology

Volume: 23, P: 1297-1299
Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT

TCR signaling initiates a signaling cascade involving the kinases Lck and Zap70 and the adaptor LAT. Weiss and colleagues discover a proline-rich motif in LAT, which facilitates interactions among Lck, LAT and Zap70 for efficient TCR signaling.

Wan-Lin Lo
Neel H. Shah
Arthur Weiss
Research18 Jun 2018
Nature Immunology

Volume: 19, P: 733-741
Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination

TCR ligation activates the tyrosine kinase ZAP-70 to phosphorylate the adapter LAT, which then coordinates TCR proximal signaling cascades. Weiss and colleagues show LAT-Y132 is critical to TCR ligand discrimination, as its phosphorylation represents a rate-limiting step in T cell activation due to a conserved glycine residue at position 131.

Wan-Lin Lo
Neel H. Shah
Arthur Weiss
Research14 Oct 2019
Nature Immunology

Volume: 20, P: 1481-1493
A liver immune rheostat regulates CD8 T cell immunity in chronic HBV infection

A liver-intrinsic mechanism is presented that suppresses effective anti-hepatitis virus B responses in mice and humans by rendering virus-specific CD8 T cells refractory to activation causing loss of effector functions.

Miriam Bosch
Nina Kallin
Percy A. Knolle
ResearchOpen Access10 Jul 2024
Nature

Volume: 631, P: 867-875
Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by augmenting TGFβ signaling through TGFBR1 stabilization

Pulmonary fibrosis is a major public health problem with unclear mechanism and limited therapeutic options. Here the authors show that a fibroblast-enriched endoplasmic reticulum protein, TXNDC5, promotes pulmonary fibrosis by stabilizing TGFBR1 and show the potential of TXNDC5 as a therapeutic target against pulmonary fibrosis.

Tzu-Han Lee
Chih-Fan Yeh
Kai-Chien Yang
ResearchOpen Access26 Aug 2020
Nature Communications

Volume: 11, P: 1-20
A voltage-gated sodium channel is essential for the positive selection of CD4⁺ T cells

Calcium signals are required for thymocyte positive selection. Allen and colleagues show that thymic selecting ligands induce SCN5a-SCN4b voltage-gated sodium channels and sustained calcium influx necessary for CD4⁺ selection.

Wan-Lin Lo
David L Donermeyer
Paul M Allen
Research29 Jul 2012
Nature Immunology

Volume: 13, P: 880-887
DCision-making in tumors governs T cell anti-tumor immunity

Francesca Alfei
Ping-Chih Ho
Wan-Lin Lo
ReviewsOpen Access21 Jul 2021
Oncogene

Volume: 40, P: 5253-5261

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