Wang et al. demonstrate that AMPK is downstream of IL-33 signaling, and feedback inhibits IL-33–induced activation of NF-κB in ILC2s. This study uncovers that adiponectin via AMPK acts as a negative regulator of ILC2s and exerts an antithermogenic effect.
Early, germinal center–independent, memory B cell responses are exquisitely sensitive to upregulation and downregulation of cell-intrinsic BAFFR signaling. However, germinal center function, including production of memory B cells, is unaffected by modulations of this pathway.
Memory B cells are long-lived components of humoral immunological memory. Müller-Winkler et al. show that the survival of MBCs is critically dependent on signaling from the BCR, BAFF, BAFFR, and IKK2 kinase.
The lysosomal protease cathepsin L uses pancreatic secretory granule protein precursors and a reverse proteolysis mechanism, transpeptidation, to generate chimeric super-epitopes specific for diabetogenic CD4 T cells.
Mice with Nfkb2 mutations that cause accumulation of the inhibitory NF-κB2/p100 (p100) precursor protein relative to the active NF-κB2/p52 (p52) product develop severe autoimmunity, whereas mice lacking p100 and p52 do not, indicating a role for p100 in pathogenesis.
Novel multi-transcription factor reporter mice were generated via CRISPR/Cas9 to dissect the developmental progression of ILC and LTi lineages. This study identifies lineage-specified precursors, indicating earlier bifurcation of ILC and LTi lineages than formerly proposed.
Enforced RANK signaling in B cells drives systemic autoimmunity and CLL development. The survival of CLL cells depends on microenvironmental RANKL, and inhibition of RANKL–RANK signaling kills murine and human CLL cells.
Single-cell analysis reveals an accumulation of short-lived disease-specific as well as non–disease-specific intestinal plasma cells in untreated and short-term–treated celiac disease. Plasma cells differ transcriptionally depending on specificity, longevity, and disease status and may contribute to formation of the celiac lesion.
The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation
Mori et al. established the composition of the LAT, CD5, and CD6 signalosomes of primary T cells. Positive and negative functions were solely assigned to the LAT and CD5 signalosomes, respectively, whereas the CD6 signalosome conveys antithetical functions with implications for autoimmune diseases.
Sustained androgen receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis
Ma et al. uncovers an essential role of AR signaling in melanoma cell expansion and tumorigenesis, with loss of AR activity inducing cellular senescence, genomic DNA breakage, a STING-dependent inflammatory cascade, and immune cell recruitment, providing an attractive venue for new combination approaches to disease management.
RIAM, which is required for conventional T cell homing and activation, is dispensable for regulatory T cell suppressive functions, thereby nominating RIAM as a focus for inhibiting conventional T cells while sparing regulatory T cells.
Brief Definitive Report
T reg cells are essential for establishing immunological tolerance, and their development in the thymus is tightly regulated. This study demonstrates that miR-155, a miRNA known for conferring T reg cell competitive fitness, can also promote T reg cell differentiation by targeting the TGFβ pathway in the thymic medulla.
Mycobacterium tuberculosis (Mtb) infects macrophages and eventually leads to their death. Zhang et al. find that type I IFN signaling contributes to the death of Mtb-infected macrophages through an apparently novel mechanism.
ST2 expression was largely dispensable for T reg cell accumulation and maintenance in tissues at steady state. However, ST2 deficiency limited to T reg cells was important in limiting the size of IL-17A–producing γδT cells in a mouse model of neuroinflammation.
JAK2V617F myeloproliferative neoplasm eradication by a novel interferon/arsenic therapy involves PML
Myeloproliferative neoplasms are partly sensitive to interferon α therapy. Dagher et al. demonstrate that arsenic trioxide sharply potentiates interferon’s ability to eliminate patients’ progenitors or disease-initiating cells from mouse models by targeting PML, an interferon target and key senescence gene.