Time marches endlessly on … but what does that mean for the immune system? Here, investigators discuss how aging impacts the immune response and how i…

Donor-specific antibodies against mismatched HLA proteins cause allograft failure, but the structural epitopes recognized by these antibodies are not well defined. Killian et al. identify immunodominant HLA-A∗01:01 epitopes that are localized specifically on the HLA crown and conserved across transplant recipients. These findings provide a framework for understanding the immunogenicity of non-self in organ transplant rejection.

Cytokines optimize and fine-tune effector T cell responses. Here, Jiang et al. utilize IL-9, with scarce receptor expression in normal tissues, to boost IL-9R engineered T cells for cancer therapy. IL-9 signaling initiates a unique STAT activation pattern, including STAT4, that modulates T cell states for effective anti-tumor responses.

Castelli et al. show that incorporating interleukin-9 (IL-9) signaling reprograms chimeric antigen receptor (CAR) T cells to expand, persist, and resist dysfunction in solid tumors. This strategy improves antitumor activity at lower doses, suggesting a promising way to enhance the effectiveness of CAR T cell therapies against solid cancers.

Immunity by Cell Press | 45 followers on LinkedIn. Cutting-edge research in immunology from around the world, and commentaries by thought leaders. | Immunity publishes the most important advances in i...

(Immunity 58, 2670–2684.e1–e10; November 11, 2025)

IgA antibodies protect mucosal surfaces from foreign antigens. Siniscalco et al. identify germinal center (GC)-independent and GC-derived pathways of gut IgA generation following immunization. Siniscalco et al. also identify IgA generation from IgG1 precursors through sequential class switching. These findings link systemic and mucosal antibodies for multi-pronged host protection.

FOXP3 is a transcription factor critical for immune homeostasis. Using a broad CRISPR toolkit, Umhoefer et al. elucidate the cis- and trans-regulatory circuitry governing FOXP3 expression in human Treg and Tconv cells, including characterization of a repressive CRE that limits expression of FOXP3 in Tconv cells.

(Immunity 58, 1040–1051; May 13, 2025)

Time marches endlessly on … but what does that mean for the immune system? Here, investigators discuss how aging impacts the immune response and how immune cells can shape the aging process, with broader implications for modifying immunity to improve not only longevity but also health span.

Until recently, the existence of long-lived IgE-secreting plasma cells was debated. Using timestamping in mouse models of type 2 inflammation, two studies in this issue of Immunity reveal the long-term persistence of IgE-secreting plasma cells in secondary lymphoid organs rather than in the bone marrow.

Wang et al. find that cell membrane stress upon viral infection induces expression and stabilization of host sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B), which, in turn, degrades cGAMP to s...

Regulatory T cells can play conflicting roles in autoimmune inflammation. In this issue of Immunity, Benamar et al. reveal that gut-microbiota-induced Notch3+ regulatory T cells migrate to the central nervous system in multiple sclerosis and transition to inflammatory Th17-like cells.

Sympathetic signaling has been implicated in colitis, but the precise circuits remain unclear. In this issue of Immunity, Sharma et al. demonstrate that myeloid cell-specific loss of DNA-demethylation dampens sympathetic signaling-driven colitis exacerbation in an IL-1β-dependent manner.

Gut microbial metabolites modulate immune responses to tumors. In this issue of Immunity, Bachem et al. demonstrate that microbiota-derived butyrate cooperates with the transcription factor Foxo1 to promote CD8+ T cell stemness and enhance responsiveness to immune checkpoint inhibitors in melanoma.

Immunosuppressive monocyte-derived macrophages are key targets in cancer therapy; however, the mechanisms of their replenishment and functional plasticity remain elusive. In a recent issue of Nature, Hedge et al. challenge the conventional view that immunosuppressive macrophages are acquired exclusively through tumor microenvironment reprogramming; instead, their study demonstrates that the developmental fate of these macrophages is predisposed in the bone marrow.

Triple-negative breast cancer (TNBC) is characterized by high risks of relapse or metastatic disease. Mattavelli et al. identify a chemokine axis that recruits immunosuppressive monocytes to tumor-dra...

Ding et al. show that allergy-associated IgE plasma cells exhibit limited accrual in the bone marrow, instead residing in other tissues for extended periods. These long-lived cells are rare and sensitive to navitoclax rather than deletion of the anti-apoptotic protein MCL1, which effectively kills other plasma cells.

Using a mouse model that selectively lacks TET2 in myeloid cells, Sharma et al. show that myeloid cells and sympathetic neurons form a signaling nexus that controls serotonin production by enterochromaffin cells, which modulates colonic inflammation. Further, physiological stress uses sympathetic cues to drive serotonin production and worsen colitis.

FOXP3 is a transcription factor critical for immune homeostasis. Using a broad CRISPR toolkit, Umhoefer et al. elucidate the cis- and trans-regulatory circuitry governing FOXP3 expression in human Tre...

The gut microbiome impacts immunity at various levels, including response to immunotherapy. Bachem et al. find that metabolic pathways shared across different microbiota constituents, including SCFA synthesis, modulate stem-like tumor-specific CD127+CD8+ T cells in the tumor-draining lymph node and impact control of melanoma.

Artyomov and colleagues provide an overview of studies on age-related changes in the human immune system, from early flow cytometry research to more recent findings using single-cell and advanced cytometry methods. They explore possible sources of discrepancies in human immune aging research and highlight major challenges that need to be addressed.