Immune mechanisms in vulvodynia: key roles for mast cells and fibroblasts.

Vulvodynia is a debilitating condition characterized by painful sensitivity to touch and pressure in the vestibular tissue surrounding the vaginal opening. It is often a "diagnosis of exclusion" of idiopathic pain made in the absence of visible inflammation or injury. However, the association between increased vulvodynia risk and a history of yeast infections and skin allergies has led researchers to explore whether immune mechanisms of dysregulated inflammation might underlie the pathophysiology of this chronic pain condition.

Unexpected suppression of tumorigenesis by c-MYC via TFAP4-dependent restriction of stemness in B lymphocytes.

The proliferative burst of B lymphocytes is essential for antigen receptor repertoire diversification during the development and selective expansion of antigen-specific clones during immune responses. High proliferative activity inevitably promotes oncogenesis, the risk of which is further elevated in B lymphocytes by endogenous gene rearrangement and somatic mutations. However, B-cell-derived cancers are rare, perhaps owing to putative intrinsic tumor-suppressive mechanisms.

Identification of a T-bet Quiescent Exhausted CD8 T Cell Subpopulation That Can Differentiate into TIM3CX3CR1 Effectors and Memory-like Cells.

Persistent Ag induces a dysfunctional CD8 T cell state known as "exhaustion" characterized by PD-1 expression. Nevertheless, exhausted CD8 T cells retain functionality through continued differentiation of progenitor into effector cells. However, it remains ill-defined how CD8 T cell effector responses are sustained in situ.

Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia.

Background: Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. Epidemiologic studies associate the risk of vulvodynia with a history of atopic disease. We used an established model of hapten-driven contact hypersensitivity to investigate the underlying mechanisms of allergy-provoked prolonged sensitivity to pressure.

The Transcription Factor AP4 Mediates Resolution of Chronic Viral Infection through Amplification of Germinal Center B Cell Responses.

B cells diversify and affinity mature their antigen receptor repertoire in germinal centers (GCs). GC B cells receive help signals during transient interaction with T cells, yet it remains unknown how these transient T-B interactions in the light zone sustain the subsequent proliferative program of selected B cells that occurs in the anatomically distant dark zone. Here, we show that the transcription factor AP4 was required for sustained GC B cell proliferation and subsequent establishment of a diverse and protective antibody repertoire.

Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression.

Failure of T cells to protect against cancer is thought to result from lack of antigen recognition, chronic activation, and/or suppression by other cells. Using a mouse sarcoma model, we show that glucose consumption by tumors metabolically restricts T cells, leading to their dampened mTOR activity, glycolytic capacity, and IFN-γ production, thereby allowing tumor progression. We show that enhancing glycolysis in an antigenic "regressor" tumor is sufficient to override the protective ability of T cells to control tumor growth.

Clonal differences in IgE antibodies affect cutaneous anaphylaxis-associated thermal sensitivity in mice.

Cellular and molecular mediators of immune responses are increasingly implicated in acute and chronic pain pathophysiologies. Here we demonstrate that passive cutaneous IgE/Ag anaphylaxis provokes increased thermal sensitivity in the hind paw tissue of mice. The murine anti-DNP IgE antibodies SPE-7 and ɛ26 are known to induce differential cytokine production in bone marrow cultured mast cells in vitro without antigen challenge.

Contact hypersensitivity to oxazolone provokes vulvar mechanical hyperalgesia in mice.

The interplay among pain, allergy and dysregulated inflammation promises to yield significant conceptual advances in immunology and chronic pain. Hapten-mediated contact hypersensitivity reactions are used to model skin allergies in rodents but have not been utilized to study associated changes in pain perception in the affected skin. Here we characterized changes in mechanical hyperalgesia in oxazolone-sensitized female mice challenged with single and repeated labiar skin exposure to oxazolone.