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TNIP1, a previously identified risk factor for autoimmunity, regulates mitochondrial autophagosomal trafficking. Missense mutations in TNIP1 disrupt this regulatory function, yielding a B cell-intrinsic predisposition for TLR7-mediated autoimmunity characterized by IgG4 autoantibodies and the expansion of age-associated B cells.

Here, the authors show that there is a pretumorigenic T_H17 subset in the intestines that can convert to being tumorigenic under the control of KLF6 and that this process can be prevented by TGFβ1 production from intestinal epithelial cells.

Vinuesa et al. identify patients with systemic autoimmunity and a TNIP1 variant that result in dysregulated B cell function. Mice with the orthologous Tnip1 mutation develop spontaneous autoimmunity associated with impaired mitophagy and autophagic silencing of proteins downstream of Toll-like receptor 7 signaling.

Why some individuals ‘resist’ infection with Mycobacterium tuberculosis (Mtb) has been an enigma. Enriched T cell phenotypes have now been linked to ‘resistance’ to Mtb infection and disease across multiple cohorts.

The G protein Gα13 is frequently lost in germinal center (GC) B cell-derived lymphomas. Mice that lack Gα13 exhibit increased proliferation of GC B cells in gut-draining lymph nodes where they go on to develop lymphomas. Dietary glutamine drives the proliferation of mucosal GC B cells that lack Gα13, potentially explaining the gut tropism of these lymphomas.

Immunological imprinting early in life has been proposed to influence the risk of infection by influenza viruses later on — but hard evidence for this has been lacking. A new study now shows how this can occur for influenza B viruses.

We constructed a humanized (THX) mouse by grafting non-γ-irradiated, genetically myeloablated immunodeficient mouse neonates with human cord blood CD34⁺ cells, followed by 17β-estradiol hormonal conditioning. THX mice develop a human lymphoid and myeloid immune system, mount mature antibacterial and antiviral neutralizing antibody responses, and are amenable to develop lupus autoimmunity.

In this Review, the authors analyze functional and dysfunctional T cell features to make sense of cancer immunotherapy efficacy and how to improve it.

Muppidi and colleagues show that loss of Gα13 drives B cell lymphomas preferentially in the mesenteric lymph nodes. They find that Gα13 is required to counteract mTORC1 and Myc signaling that is driven by the availability of dietary glutamine.

We performed transcriptional and chromatin accessibility profiling of T_H17 cells to distinguish the pathways that regulate pathogenic versus non-pathogenic T_H17 cell subsets. We show that T_H17 cell functional heterogeneity is linked to distinct regulatory programs that are shared between T_H17 cells and other CD4⁺ T cell states. BACH2 was identified as a key regulator of T_H17 cell-mediated autoimmunity.

In this study, Uldrich and colleagues describe the crystal structure of the Vγ9Vδ2 T cell antigen receptor (TCR) interacting with BTN2A1 and demonstrate the existence of a second ligand that co-binds to a distinct epitope on Vγ9Vδ2 TCR. Using these data, the authors suggest a model of Vγ9Vδ2 TCR activation in which BTN2A1 and BTN3A1 are tethered to each other at the steady state, and must disengage to allow TCR binding.

The EMBO workshop ‘Pathogen Immunity and Signaling’, held in San Servolo, Italy, from 8 to 12 April 2024, aimed to discuss cutting-edge advances in the understanding of antimicrobial defense mechanisms.

Regulating the balance between T_H17 cells that drive autoimmune inflammation and nonpathogenic T_H17 cells is critical for limiting autoimmune pathology. Here, the authors extensively characterize these two cell states at the transcriptomic and epigenetic levels and show how BACH2 is protective in this context.

In this Review, the author outlines the complex immunology of systemic lupus erythematosus and how to treat it.

Seshadri, Davis and colleagues show that individuals who do not develop an infection with Mycobacterium tuberculosis (Mtb), despite exposure to the bacteria and expansion of CD4⁺ T cell clones specific to Mtb antigens, show enrichment of T_H17 cell and T regulatory functional programs.

The thymus harbors a complex constitutively active inflammatory network with innate-like T cells representing one of its central nodes. Here, the authors show that these cells can induce tolerance to inflammation-associated self-antigens, a class of molecules that otherwise largely mirrors the spatial and temporal distribution of pathogen-derived antigens.

Our study shows that each stimulation experienced by memory B cells is epigenetically recorded in an IRF4-dependent manner, which determines the relative levels of BLIMP1 and BACH2 in B cells, and in turn dictates the likelihood that a memory B cell enters a germinal center or becomes a plasma cell after re-stimulation.

Extrafollicular and germinal center reactions are considered to represent sequential phases of a primary B cell response. A study now demonstrates the ability of autocrine IL-12 to promote extrafollicular differentiation into plasmablasts, while inhibiting germinal center responses.

Innate lymphoid cells (ILCs) exhibit remarkable plasticity, which makes using definitive markers to distinguish non-cytotoxic ILC1s and NK cells across different tissues difficult. New research now shows how the tissue microenvironments imprint diverse phenotypes that result in ILC1s and NK cells imitating each other.