Obesity alters monocyte developmental trajectories to enhance metastasis
Obesity is associated with enhanced breast cancer mortality, yet the mechanisms underlying this relationship remain poorly understood. McDowell et al. provide insight into the role of obesity on myeloid-driven cancer metastasis by identifying how monocyte development is skewed to promote prometastatic neutrophil effector functions.
The Src–ZNRF1 axis controls TLR3 trafficking and interferon responses to limit lung barrier damage
E3 ubiquitin ligase ZNRF1 is activated by c-Src kinase following TLR3 activation and, in turn, promotes TLR3 ubiquitination and trafficking to lysosomes for degradation. This leads to properly regulated interferon production and alveolar barrier repair to prevent secondary bacterial superinfection.
OX40L-expressing recombinant modified vaccinia virus Ankara induces potent antitumor immunity via reprogramming Tregs
This study shows that intratumoral injection of engineered non-replicative recombinant modified vaccinia virus Ankara depletes and reprograms tumor-infiltrating regulatory T cells via OX40L–OX40 interaction and IFNAR signaling to enhance antitumor immunity.
TRAF3–EWSR1 signaling axis acts as a checkpoint on germinal center responses
Li et al. reveal that the TRAF3–EWSR1 signaling axis serves as a critical checkpoint in the regulation of induced germinal center (GC) responses and immunoglobulin production. This signaling axis acts as a negative regulator of Bcl6 upregulation, which in turn negatively affects GC B cell generation and IgG production.
SARS-CoV-2 infection and recovery in children: Distinct T cell responses in MIS-C compared to COVID-19
Identification of an anergic BND cell–derived activated B cell population (BND2) in young-onset type 1 diabetes patients
The role of B cells in T1D remains poorly understood. We identified an activated B cell subset that is enriched in insulin reactivity and increased in the blood and pLN of T1D donors. This subset has capacity to secrete antibodies and potential to serve as APCs to T cells.
Diet-mediated constitutive induction of novel IL-4+ ILC2 cells maintains intestinal homeostasis in mice
A novel ILC2 subset was identified in the mouse intestine that constitutively expresses IL-4. Although the absence of the gut microbiota had marginal effects, feeding mice with a vitamin B1-deficient diet compromised the number of intestinal IL-4+ ILC2s.
Dietary protein shapes the profile and repertoire of intestinal CD4+ T cells
Lockhart et al. demonstrate that exposure to food protein drives an antigen-specific CD4+ T cell response characterized at steady state by accumulation at the intestinal epithelium and tissue-specialized transcriptional imprinting. This process is disrupted upon either allergic sensitization or tolerance.
Intracellular trafficking of HLA-E and its regulation
Understanding the unique features of immune functions of HLA-E to inform future clinical exploitation requires detailed knowledge of HLA-E transport. He et al. characterize the basic trafficking patterns of HLA-E within cells and how this trafficking is regulated.
CD30 co-stimulation drives differentiation of protective T cells during Mycobacterium tuberculosis infection
Foreman et al. find CD30 is preferentially expressed on granuloma T cells in Mtb-infected macaques. In mice, CD30 drives T cell differentiation and is required for host survival of Mtb infection, showing T cell immunity to Mtb requires CD30-dependent co-stimulation.
Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production
Kang et al. identify a novel secretory subset of myeloid-biased multipotent progenitors, MPP3, which enforces myeloid lineage differentiation through lineage-priming and cytokine secretion and serves an essential regulatory function to amplify myeloid cell production in stress and disease conditions.
Brief Definitive Report
Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation
Using antigen-induced arthritis (AIA) model, Zec et al. show that synovial lining macrophages undergo IRF5-dependent activation and produce CXCL1 as a result of antigen recognition. Consequently, neutrophils are preferentially recruited in the synovial lining niche at the onset of inflammation.
TB granuloma: CD30 co-stimulation for CD4+ T cell co-operation
In this issue of JEM, Foreman et al. report that, in tuberculosis granuloma, CD4 T effector cells require signals through CD30, potentially provided co-operatively by other T cells, to completely differentiate and protect against disease.