In this issue of JEM, Nadkarni et al. identify CARD8 as an innate sensor triggered by coxsackievirus B3 proteases to drive pyroptosis of aortic endothelial cells and cardiac myocytes, fueling viral replication and heart inflammation.
Found in Translation
Laura Chiossone and Eric Vivier discuss the recent advances of NK cell therapies in cancer, which include adoptive NK cell therapies and the harnessing of NK cells using immune checkpoint inhibitors, NK cell engagers, cytokines, and the combination thereof.
Brief Definitive Reports
Nadkarni et al. show that human endothelial cells (EC) engage both NLRP1 and CARD8 inflammasomes. CARD8 is activated by Coxsackie B3 protease-mediated N-terminal cleavage. Knocking out CARD8 attenuates CVB3 propagation and dampens inflammation in a cellular model of viral myocarditis.
SARS-CoV-2 breakthrough infection in vaccinees induces virus-specific nasal-resident CD8+ and CD4+ T cells of broad specificity
Virus-specific T cells in the nasal cavity might provide an immediate layer of protection against SARS-CoV-2. This study detected SARS-CoV-2–specific nasal-resident T cells in vaccinees only after infection, highlighting the significance of nasal challenge in the formation of antiviral immunity at the site of infection.
Technical Advances and Resources
In this study, the authors perform a genome-wide methylation analysis to define epigenetic signatures for murine ILCs and to assess similarities and differences to CD4+ T cells. Models of IL-33–mediated inflammatory challenge reveal tissue-specific epigenetic changes within ILC2 signature regions.
Wang et al. compare antibody immune responses following different COVID-19 vaccination regimens. Their detailed immunological and structural analysis revealed significant differences that can inform improved vaccination strategies for the prevention of COVID-19 and other respiratory viral infections of pandemic potential.
The present study reveals that glucocorticoids promote the production of IgE by rare B cells in the mesenteric lymph nodes in the absence of experimentally administered antigens.
The signals that control the differentiation of Tcf-1+ CD8+ T cells are not entirely known. Here, the authors find that TGF-β promotes lymphoid residency and inhibits the effector differentiation of Tcf-1+ T cells partially via controlling the expression of α4 integrins.
TGF-β regulates the stem-like state of PD-1+ TCF-1+ virus-specific CD8 T cells during chronic infection
This study demonstrates the role of TGF-β on virus-specific CD8 T cell differentiation during chronic LCMV infection. TGF-β maintains the stem-like state of TCF-1+ CD8 T cells and promotes terminal differentiation of exhausted cells by suppressing effector- and proliferation-associated programs.
Thymic epithelial cells present self-peptide/MHC complexes to developing T cells. Here, Postoak et al. describe a novel role for the lipid kinase Vps34 in controlling the production of self-peptides optimized for selection of CD4 but not CD8 T cells.
A dysregulated sebum–microbial metabolite–IL-33 axis initiates skin inflammation in atopic dermatitis
This study demonstrates that a dysregulated sebum–microbial metabolite–IL-33 axis is involved in the pathogenesis of atopic dermatitis, possibly by playing an initiating role in the induction of skin inflammation.
Impaired IL-23–dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency
This study characterizes three novel forms of autosomal recessive human TYK2 deficiency. Impairment of IL-23–dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with any of the five known forms of autosomal recessive TYK2 deficiency.
Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing
Kessler et al. identify aberrant DNA recognition by cGAS/STING and IFN-I production by inflammatory macrophages as a driver of severe ANCA-associated vasculitis. Pharmacological interventions blocking this pathway ameliorate disease and accelerate recovery, identifying potential targets for therapeutic intervention in patients.
This study demonstrates the regulatory pathways closely associated with a metastatic cancer signature regulated by HER2 in invasive IPF lung fibroblasts. Manipulation of HER2 in vitro and in vivo shows that HER2 signaling is a key driver of fibroblast invasion and progressive lung fibrosis.