Discussion on the divergent immunological effects of pregnancy on T cell and humoral immunity, how prior pregnancy impacts responses upon alloantigen re-encounter in the context of solid organ transplantation, and potential strategies for controlling pregnancy-dependent allosensitization.
We review our current understanding of adaptive immune responses to the fetoplacental allograft, emphasizing the divergent responses observed for trophoblast- versus fetal blood cell–derived antigens. We suggest these divergent responses arise from cell type–specific glycosylation programs that impart trophoblast-derived antigens with immunosuppressive properties.
Brief Definitive Reports
Intermittent prednisone treatment in mice promotes exercise tolerance in obesity through adiponectin
Chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress. In contrast, this study reports that intermittent, once-weekly dosing of the glucocorticoid prednisone promotes exercise tolerance and muscle metabolism in mice with diet-induced obesity through adiponectin elevation.
Cutaneous vaccinia virus infection induces VEGFR2-dependent dermal lymphatic capillary zippering and lymph node lymphangiogenesis, which exacerbates tissue edema, sequesters virus, and promotes CD8+ T cell responses. The lymphatic network is therefore an active barrier that contributes to innate host defense.
Technical Advances and Resources
Effective and precise gene editing of T lymphocytes is critical for advancing our understanding of T cell biology and the development of next-generation cellular therapies. The authors report a simple and efficient method for nonviral CRISPR/Cas9-based editing of T lymphocytes using plasmid donor DNA.
FNIP1 regulates adipocyte browning and systemic glucose homeostasis in mice by shaping intracellular calcium dynamics
Metabolically beneficial beige adipocytes offer tremendous potential to treat obesity and metabolic diseases. Yin et al. show that FNIP1 acts as a negative regulator of beige adipocyte thermogenesis to control systemic glucose homeostasis through modulating the ER Ca2+-ATPase SERCA.
EP3 enhances adhesion and cytotoxicity of NK cells toward hepatic stellate cells in a murine liver fibrosis model
Tao et al. describe that activation of E-prostanoid 3 receptor (EP3) ameliorates injury-induced liver fibrosis through promoting NK cell adhesion and killing of activated hepatic stellate cells in mice, indicating that EP3 may serve as a potential therapeutic target for liver fibrosis.
This study reports the first known family with pulmonary fibrosis carrying a heterozygous POT1 mutation. The family displays short telomeres, short telomere phenotypes, and genetic anticipation. The data suggest POT1(L259S) is a pathogenic driver of IPF and provide insights into gene therapy options.
This study demonstrates that E3 ubiquitin ligase autocrine motility factor receptor (AMFR) drives lung inflammation in asthma through promoting alveolar macrophage–derived GM-CSF production, and may emerge as a new potential drug target for asthma therapy.
Monocytes transition to macrophages within the inflamed vasculature via monocyte CCR2 and endothelial TNFR2
Changes in monocyte state occur during inflammation. We show that following glomerular inflammation, CCR2+CX3CR1+ double-positive monocytes, which are preferentially recruited, acquire macrophage features while still within the renal vasculature, in a process requiring CCR2 on monocytes and TNF-TNFR2–activated endothelial cells.
miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease
miR-374a-5p is a central regulator in IBD, as its down-regulation increases the expression of a module of key inflammatory mediators. miR-374a-5p up-regulation in vitro ameliorated the increased monocyte-driven inflammation by reducing proinflammatory mediators, migration capacity, and T cell activation. miR-374a-5p has a therapeutic potential in immune-mediated diseases.
Mann et al. report the accrual of a population of IL-17–producing γδT cells shortly after acute injury of murine skeletal muscle. This microbiota-dependent population promotes muscle repair in an IL-17A– and neutrophil-dependent manner.
CCR2/CCR5 inhibitor permits the radiation-induced effector T cell infiltration in pancreatic adenocarcinoma
This preclinical study showed that CCR2/CCR5 dual-antagonist counteracts radiation-induced suppressive signals in myeloid cells and upregulates the effector T cell pathway and supported the ongoing clinical trial of the combination therapy of radiation, CCR2/CCR5 dual-antagonist, and anti–PD-1 antibody for locally advanced pancreatic cancer.
The CD3ζ adaptor structure determines functional differences between human and mouse CD16 Fc receptor signaling
CD16 is a potent activating receptor in human NK cells but is weakly responsive in mouse NK cells. Aguilar et al. demonstrate that this is due to differences in amino acids in the transmembrane of CD3ζ that facilitate receptor assembly and function.
Chen et al. uncovered the transcriptional, developmental, and functional heterogeneity of ILC1s and demonstrated the dynamic changes that occur in ILC1 subsets from different origins during ontogeny, which correspond to their different functional roles, facilitating adaptation to age-related immune demands.
Lymph node fibroblastic reticular cells regulate differentiation and function of CD4 T cells via CD25
Our findings demonstrate a previously unknown mechanism for the IL-2 receptor signaling mediated by LN-TRCs for differentiation of naive CD4 T cells. Particularly, reduced CD25 expression on the surface of LN-TRCs exacerbates autoimmune phenotypes through enhanced differentiation of Th17 cells.