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JEM Clinical Immunology Collection 2021
A selection of the latest breakthroughs to coincide with the
FOCIS 2021 Virtual Annual Meeting
Altered T cell tolerance to a single self-ligand
Tumor-adipose-muscle crosstalk via IL6 in cachexia
Human myeloid cells that promote visceral melanoma

RUP response to COVID-19 crisis: Learn about the steps we are taking and find relevant content.

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Newest Articles

Article

| June 18 2021

MKRN3-PABPC1 tumor suppression axis in NSCLC

Ke Li, Xufen Zheng, Hua Tang, Yuan-Sheng Zang, Chunling Zeng, Xiaoxiao Liu, Yanying Shen, Yuzhi Pang, Simin Wang, Feifei Xie, Xiaojing Lu, Yuxiang Luo, Zhang Li, Wenbo Bi, Xiaona Jia, Tao Huang, Rongqiang Wei, Kenan Huang, Zihao Chen, Qingchen Zhu, Yi He, Miaoying Zhang, Zhizhan Gu, Yichuan Xiao, Xiaoyang Zhang, Jonathan A. Fletcher, Yuexiang Wang

Recurrent inactivated mutations in central precocious puberty-associated gene MKRN3 lead to lung cancer proliferation and progression through PABPC1 ubiquitination–mediated global protein synthesis. MKRN3 is a bona fide tumor suppressor, and MKRN3-PABPC1 deregulation represents a key pathway in NSCLC oncogenesis.

Article

| June 17 2021

Defining the mechanism of STAT3 dominance in AD-HIES

Takaki Asano, Joëlle Khourieh, Peng Zhang, Franck Rapaport, András N. Spaan, Juan Li, Wei-Te Lei, Simon J. Pelham, David Hum, Maya Chrabieh, Ji Eun Han, Antoine Guérin, Joseph Mackie, Sudhir Gupta, Biman Saikia, Jamila E.I. Baghdadi, Ilham Fadil, Aziz Bousfiha, Tanwir Habib, Nico Marr, Luckshman Ganeshanandan, Jane Peake, Luke Droney, Andrew Williams, Fatih Celmeli, Nevin Hatipoglu, Tayfun Ozcelik, Capucine Picard, Laurent Abel, Stuart G. Tangye, Stéphanie Boisson-Dupuis, Qian Zhang, Anne Puel, Vivien Béziat, Jean-Laurent Casanova, Bertrand Boisson

Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) are heterozygous for rare STAT3 variants. The mechanism of dominance was recently questioned. The authors show that both in-frame and out-of-frame STAT3 variants underlie AD-HIES by negative dominance and not haploinsufficiency.

Technical Advances and Resources

| June 16 2021

Single-cell analysis of spinal cord injury

Lindsay M. Milich, James S. Choi, Christine Ryan, Susana R. Cerqueira, Sofia Benavides, Stephanie L. Yahn, Pantelis Tsoulfas, Jae K. Lee

This study uses single-cell RNA sequencing to investigate the transcriptional heterogeneity of all cell types known to comprise the acutely injured spinal cord in mice. The authors investigate both cell subtype heterogeneity and potential signaling interactions between myeloid, vascular, and macroglia cells.

Article

| June 15 2021

Multi-omic profiling across COVID-19 severity

Aaron J. Wilk, Madeline J. Lee, Bei Wei, Benjamin Parks, Ruoxi Pi, Giovanny J. Martínez-Colón, Thanmayi Ranganath, Nancy Q. Zhao, Shalina Taylor, Winston Becker, Stanford COVID-19 Biobank, David Jimenez-Morales, Andra L. Blomkalns, Ruth O’Hara, Euan A. Ashley, Kari C. Nadeau, Samuel Yang, Susan Holmes, Marlene Rabinovitch, Angela J. Rogers, William J. Greenleaf, Catherine A. Blish

Single-cell profiling demonstrates multifarious dysregulation of innate immune phenotype associated with COVID-19 severity. Severe COVID-19 is associated with hyperactivation of neutrophils and NK cells, while monocytes take on tolerogenic phenotypes. Meanwhile, mild COVID-19 is associated with limited, or rapidly resolved, immune perturbation.

Article

| June 15 2021

Dynamic innate immunity in SARS-CoV-2 infection

Nagarjuna R. Cheemarla, Timothy A. Watkins, Valia T. Mihaylova, Bao Wang, Dejian Zhao, Guilin Wang, Marie L. Landry, Ellen F. Foxman

SARS-CoV-2 replication in the upper respiratory tract initiates infection and leads to viral transmission. Cheemarla et al. show that a dynamic innate immune response can curtail viral replication early in infection, and that recent exposure to rhinovirus accelerates innate defenses and blocks viral replication.

Brief Definitive Report

| June 11 2021

STAT3-GOF disrupts CD8 tolerance to promote T1D

Jeremy T. Warshauer, Julia A. Belk, Alice Y. Chan, Jiaxi Wang, Alexander R. Gupta, Quanming Shi, Nikolaos Skartsis, Yani Peng, Jonah D. Phipps, Dante Acenas, Jennifer A. Smith, Stanley J. Tamaki, Qizhi Tang, James M. Gardner, Ansuman T. Satpathy, Mark S. Anderson

Human STAT3 gain-of-function (GOF) mutations are linked to type 1 diabetes (T1D). This study establishes a STAT3-GOF mouse model that recapitulates the human T1D phenotype. STAT3-GOF drives cytotoxic CD8+ T cells that are resistant to terminal exhaustion, epigenetically distinct, and sufficient to accelerate T1D development.

Brief Definitive Report

| June 09 2021

VISTA activates monocytes and implicates Syndecan-2

Bryan M. Rogers, Laura Smith, Zoltan Dezso, Xu Shi, Enrico DiGiammarino, Denny Nguyen, Sunantha Sethuraman, Pingping Zheng, Donghee Choi, Dong Zhang, Andrew Nguyen, Kathleen McGuire, Wei Liu, Namjin Chung, Debra T. Chao, Shiming Ye, Gabriel R. Starbeck-Miller

VISTA biology has yet to be fully resolved despite much enthusiasm to define it as an immune checkpoint protein. Here, we show that VISTA antibodies can singly activate human monocytes and provide evidence that Syndecan-2 can regulate VISTA interactions.

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TNFR1 was found to cause skin inflammation in mice with epidermal keratinocyte-specific ablation of IKK2 or of both the NF-kB subunits RelA and cRel by triggering RIPK1-dependent, RIPK3-MLKL–mediated necroptosis of keratinocytes.
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Volume 218,

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June 7, 2021

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Reviews & Opinions

Insights

| June 16 2021

Inhibiting BRD4 to generate BETter T cell memory

Moujtaba Y. Kasmani, Weiguo Cui

BRD4 is a bromodomain-containing protein that binds acetylated histones to regulate transcription. In this issue of JEM, Milner et al. show that BRD4 plays a critical role in the effector function of CD8 T cells responding to infection and cancer.

Review | Hematopoietic Stem Cells Focus

| June 15 2021

Technologies for cell signaling analysis

Tobias Kull, Timm Schroeder

Cells constantly sense their environment to adapt their behavior to changing needs. Kull and Schroeder discuss the requirements, potential, and limitations of current technologies for quantification and manipulation of cellular signaling in the context of inflammatory signaling in hematopoietic cells.

Review | Hematopoietic Stem Cells Focus

| June 15 2021

Effects of inflammation on HSC biology

Francisco Caiado, Eric M. Pietras, Markus G. Manz

This review summarizes and integrates current views on the contribution of inflammatory signals derived from multiple sources to hematopoietic stem cell function and its long-term implications on mutational selection and clonal expansion during aging.

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Special Collections

The Year in Experimental Medicine

Our annual Best of JEM series, featuring articles that were of great interest to our readers..

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Swift and confidential updates to author names at any time and for any reason. Learn more

JEM Clinical Immunology Collection 2021 A selection of the latest breakthroughs to coincide with the FOCIS 2021 Virtual Annual Meeting

Altered T cell tolerance to a single self-ligand

Tumor-adipose-muscle crosstalk via IL6 in cachexia

Human myeloid cells that promote visceral melanoma

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JEM Clinical Immunology Collection 2021
A selection of the latest breakthroughs to coincide with the
FOCIS 2021 Virtual Annual Meeting