- NLRP3 promotes pancreatic oncogenesis
Daley et al. show that NLRP3 signaling in macrophages drives their immune-suppressive phenotype in the pancreatic tumor microenvironment and potentiates tolerogenic T cell differentiation. Conversely, targeting NLRP3 protects against pancreatic oncogenesis and is associated with immunogenic reprograming within the tumor.
- Tissue adaptation in gut immunity and tolerance
Faria et al. discuss the concept that immune cells undergo specialized adaptation to tissue-specific conditions and its potential implications for tolerance and immunity.
- Heterogeneity of phagocytic macrophages
Macrophages are important for tissue function, and adapt phenotypically to each tissue by factors produced locally. A-Gonzalez et al. now show that phagocytosis of unwanted cells additionally contributes to imprinting macrophage heterogeneity, thus promoting tissue homeostasis.
- TSLP-DC promote human Tfh differentiation
T follicular helper cells (Tfh) are implicated in various pathological conditions, but how they differentiate in Th2-skewed environments is unknown. Pattarini et al. delineate a pathway for human Tfh differentiation induced by TSLP through OX40L, relevant to atopic dermatitis.
- Splenic neutrophils eradicate S. pneumoniae
The spleen is integral for protection against encapsulated bacteria. Using intravital imaging, Deniset et al. demonstrate that resident neutrophil and macrophage populations in the spleen coordinate the rapid clearance of Streptococcus pneumoniae, ensuring sufficient time for subseqent protective antibody production.
- Location in the spleen dictates the function of murine neutrophils
In this issue, Deniset et al. provide new data that extend our knowledge on the mechanisms whereby Streptococcus pneumoniae is cleared by the spleen. The authors identify novel populations of murine splenic neutrophils that localize in the red pulp and the marginal zone. During the acute phases of S. pneumoniae infection, these populations of splenic neutrophils act in concert with specialized macrophage and B cell populations to provide very rapid innate immune protection.
- Genetic landscape of EATL
Enteropathy-associated T cell lymphoma (EATL) is the most common oncologic complication of celiac disease. Moffitt and colleagues identify novel EATL-defining mutations in SETD2, as well as clinically relevant mutations in the JAK-STAT pathway.
- Ultrasensitive detection of IFNα in human diseases
Rodero et al. report the direct quantification of IFNα protein in monogenic interferonopathies, autoimmunity, and infectious disease states, made possible by the combination of digital ELISA and high-affinity autoantibodies isolated from APECED patients, revealing differential levels and cellular sources dependent on underlying pathology.
- MINK1: The missing link between ROS and its inhibition of Th17 cells
In this issue of JEM, Fu et al. identified the kinase Mink1 as a novel negative regulator of Th17 cell generation. Mink1, activated by reactive oxygen species (ROS), prevents TGF-β activation of Smad2, therefore limiting Th17 cell differentiation.