In this issue of JEM, Manz and Volta discuss the study by Marone et al. that proposes a target-epitope resistance editing strategy in healthy hematopoietic stem cells to prevent immunotherapy-derived myelotoxicity in the context of AML.
In this issue of JEM, D.L. Barber discusses the study by Winchell and Nyquist et al. showing that CD8αα+ lymphocytes have a major role in the innate suppression of Mycobacterium tuberculosis growth in macaques’ lungs.
In this issue of JEM, Singh et al. show that Rorγt+ regulatory T cells suppress pathogenic IFN-γ responses to control Staphylococcus aureus growth and limit S. aureus– and Leishmamia braziliensis–associated immunopathology at the skin barrier.
In this issue of JEM, Çakan et al. explore a CXCL4-mediated mechanism by which TLRs cause autoimmunity in human B cells, breaching bone marrow tolerance.
In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher. As well as being able to celebrate the positives of becoming an independent researcher, we would also like to use this platform to discuss the unique challenges they face as women scientists in their respective scientific environments.
Brief Definitive Reports
The authors describe the first patient treated with a new cell therapy consisting of Tregs purified from pediatric thymus (thyTreg). 2 years after thyTreg administration in a heart-transplant child, no adverse effects have been reported and the peripheral Treg pool is preserved.
The authors provide evidence that citrullinated peptides induce immune tolerance in cognate CD4+ T cells in healthy individuals. This tolerance may be a barrier to induction of rheumatoid arthritis.
Both B cells and TLR signaling have been implicated in lupus pathogenesis. B cell–specific MyD88, when targeted after disease onset resulted in the stabilization of autoantibody levels and amelioration of disease, suggesting a possible therapeutic efficacy of targeting MyD88-related pathways in the treatment of SLE.
Technical Advances and Resources
PD-1 engagement by T cells inhibits distinct antigen-evoked signals in a nonlinear manner, strongly influenced by the nature of available TCR ligands.
This work demonstrates that engineering a single amino acid substitution into the cell surface protein CD123 in hematopoietic stem cells protects them from targeted immunotherapies. Transplantation of the modified stem cells may enable posttransplant therapy to reduce disease recurrence.
This study demonstrates that CD8+ lymphocytes play a critical role in limiting early Mycobacterium tuberculosis infection and spread within lungs and lymph nodes in a non-human primate model. Vaccines that induce cytotoxic CD8 lymphocytes may provide better protection against tuberculosis.
Foxp3+ regulatory T cells are vital for skin homeostasis, and this research involving mice and Leishmania braziliensis patients reveals that Treg levels function as a rheostat, controlling bacteria in the skin and influencing whether bacteria induce IL-17 or IFN-γ–mediated immunopathology.
TLR9 displays an important early tolerogenic function essential for central B cell tolerance, and CXCL4 inhibits TLR9 function in B cells from SSc patients by sequestering TLR9 ligands away from endosomal TLR9, leading to autoreactive B cell and autoantibody production.
In vivo deletion in the mouse reveals an essential role of the Pax5 C-terminal domain in B cell commitment and development by activating or repressing most Pax5 target genes. This domain induces chromatin changes by interacting with chromatin-remodeling and histone-modifying complexes.
Song et al. report that TIMP1 is a key regulatory factor produced by post-infection hosts that sustains long-term myeloid-biased inflammatory hematopoiesis.
Titcombe et al. report that the non-classical AP-1 nuclear factor BATF is essential for the growth arrest and yet continued survival of tolerant T cells that have entered an anergic state based on its ability to activate anergy genes and repress BIM-dependent cell death.
Effector ILC2s retain phenotypic flexibility after hematogenous trafficking and can adapt to distant tissue niches, irrespective of their origin. Retinoic acid signaling is an important driver of intestine-specific ILC2 adaptation with functional implications for acute helminth infections.
Maternal diet during early gestation influences postnatal taste activity–dependent pruning by microglia
Microglia aid in refining central gustatory circuits during normal postnatal development. This process is arrested by merely restricting the mother’s dietary sodium during a limited, early prenatal period when microglia progenitors migrate from the yolk sac to the brain.
Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells
This study characterizes an adult retinal pigment epithelial stem cell–derived cell product through transplantation in RCS rats and bulk and single-cell RNA sequencing, identifying distinct subpopulations and a predictive lncRNA marker (TREX) affecting cell integration and vision rescue in rats.
Expressions of Concern