Distal Immunization and Systemic Cytokines Establish a Transient Immune Alert State in the Intestine.

Conventionally, immune responses are studied in the context of inflamed tissues and their corresponding draining lymph nodes (LNs). However, little is known about the effects of systemic inflammatory signals generated during local inflammation on distal tissues and nondraining LNs. Using a mouse model of cutaneous immunization, we found that systemic inflammatory stimuli triggered a rapid and selective distal response in the small intestine and the mesenteric LN (mesLN).

Identification of Intestinal Lamina Propria Plasma Cells by Surface Transmembrane Activator and CAML Interactor Expression.

Plasma cells secrete an abundance of Abs and are a crucial component of our immune system. The intestinal lamina propria harbors the largest population of plasma cells, most of which produce IgA. These Abs can bind to beneficial gut bacteria to reinforce intestinal homeostasis and provide protection against enteric pathogens.

Single-cell Profiling Uncovers a -Expressing Metaplastic Gastric Cell Type Sustained by -driven Inflammation.

Unlabelled: Mechanisms for ()-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant infection and induction of constitutively active KRAS (+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA sequencing showed that +KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin and the growth factor amphiregulin Flow cytometry and IHC-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T-cell inflammation.

Twice the tolerance.

A gut microbiota-derived antigen elicits distinct subsets of regulatory T cells to suppress inflammation in mice.

Cytokine therapy in necrotizing enterocolitis: A promising treatment for preterm infants.

Necrotizing enterocolitis (NEC) is an intestinal disorder that disproportionately affects premature infants and lacks in effective therapeutics. Mihi and colleagues demonstrated that the cytokine interleukin-22 promotes intestinal epithelial regeneration and reduces disease severity in an experimental model of NEC.

Nourishing the Microbiota to Promote Mucosal Immunity.

Childhood undernutrition is associated with dysbiosis and dampened vaccine responses. Understanding how nutrients influence the microbiota and immunity is critical for vaccine efficacy. In this issue of Cell Host & Microbe, Di Luccia et al.

B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota.

B-1a cells play an important role in mediating tissue homeostasis and protecting against infections. They are the main producers of 'natural' IgM, spontaneously secreted serum antibodies predominately reactive to self antigens, like phosphatidylcholine (PtC), or antigens expressed by the intestinal microbiota. The mechanisms that regulate the B-1a immunoglobulin (Ig) repertoire and their antibody secretion remain poorly understood.

induces intestinal adaptive immune responses during homeostasis.

Intestinal adaptive immune responses influence host health, yet only a few intestinal bacteria species that induce cognate adaptive immune responses during homeostasis have been identified. Here, we show that , an intestinal bacterium associated with systemic effects on host metabolism and PD-1 checkpoint immunotherapy, induces immunoglobulin G1 (IgG1) antibodies and antigen-specific T cell responses in mice. Unlike previously characterized mucosal responses, T cell responses to are limited to T follicular helper cells in a gnotobiotic setting, without appreciable induction of other T helper fates or migration to the lamina propria.

Sex Bias in Sepsis.

Though critical for preventing fatal sepsis, the mechanisms mediating the capture of bloodstream bacteria are incompletely understood. New work by Zeng et al. (2018) demonstrates that estrogen-regulated innate antibodies protect females and newborns from death following bloodstream infection with enteropathogenic Eschericia coli.

Living in Peace: Host-Microbiota Mutualism in the Skin.

Commensal microbes colonize the skin where they promote immune development and prevent infection without inducing damaging inflammatory responses. In this issue of Cell Host & Microbe, Scharschmidt et al. (2017) show that during hair follicle development, commensals induce regulatory T cell migration to the skin to ensure cutaneous homeostasis.

Maternal IgG and IgA Antibodies Dampen Mucosal T Helper Cell Responses in Early Life.

To maintain a symbiotic relationship between the host and its resident intestinal microbiota, appropriate mucosal T cell responses to commensal antigens must be established. Mice acquire both IgG and IgA maternally; the former has primarily been implicated in passive immunity to pathogens while the latter mediates host-commensal mutualism. Here, we report the surprising observation that mice generate T cell-independent and largely Toll-like receptor (TLR)-dependent IgG2b and IgG3 antibody responses against their gut microbiota.

Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection.

Regulatory T (T reg) cells play an essential role in preventing autoimmunity but can also impair clearance of foreign pathogens. Paradoxically, signals known to promote T reg cell function are abundant during infection and could inappropriately enhance T reg cell activity. How T reg cell function is restrained during infection to allow the generation of effective antiviral responses remains largely unclear.

TLR5 stops commensals in their tracks.

IgA antibodies help maintain intestinal immune homeostasis with resident commensal species; however, the precise mechanisms regulating IgA induction and the epitopes recognized by these antibodies remain incompletely understood. In this issue of Cell Host & Microbe, Tyler et al. (2013) demonstrate that TLR5-dependent induction of anti-flagellin antibodies prevents commensal association with the intestinal mucosa by limiting bacterial motility.

T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor β2.

Foxp3(+) regulatory T (Treg) cells limit inflammatory responses and maintain immune homeostasis. Although comprised of several phenotypically and functionally distinct subsets, the differentiation of specialized Treg cell populations within the periphery is poorly characterized. We demonstrate that the development of T-bet(+) Treg cells that potently inhibit T helper 1 (Th1) cell responses was dependent on the transcription factor STAT1 and occurred directly in response to interferon-γ produced by effector T cells.

Phenotypical and functional specialization of FOXP3+ regulatory T cells.

Forkhead box P3 (FOXP3)(+) regulatory T (T(Reg)) cells prevent autoimmune disease, maintain immune homeostasis and modulate immune responses during infection. To accomplish these tasks, T(Reg) cell activity is precisely controlled, and this requires T(Reg) cells to alter their migratory, functional and homeostatic properties in response to specific cues in the immune environment. We review progress in understanding the diversity of T(Reg) cells, T(Reg) cell function in different anatomical and inflammatory settings, and the influence of the immune environment on T(Reg) cell activity.

The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation.

Several subsets of Foxp3(+) regulatory T cells (T(reg) cells) work in concert to maintain immune homeostasis. However, the molecular bases underlying the phenotypic and functional diversity of T(reg) cells remain obscure. We show that in response to interferon-gamma, Foxp3(+) T(reg) cells upregulated the T helper type 1 (T(H)1)-specifying transcription factor T-bet.