Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33.

Background: Asthma in a mouse model spontaneously resolves after cessation of allergen exposure. We developed a mouse model in which asthma features persisted for 6 months after cessation of allergen exposure.

Objective: We sought to elucidate factors contributing to the persistence of asthma.

Mechanisms of sustained signalling in asthma.

Purpose Of Review: The role of immunological memory formation focusing upon Th2 inflammatory responses in asthma is well supported and reviewed previously. Here, we review data supporting the establishment of a tissue-based signalling memory utilizing examples of in-vitro, in-vivo and clinical reports of sustained extracellular signal regulated kinase 1/2 (ERK1/2) activation in asthma.

Recent Findings: Endosomal recycling of receptors contributes to chronic signalling activation, presumably through increased receptor availability.

Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice.

During peripheral immune activation caused by an infection or an inflammatory condition, the innate immune response signals to the brain and causes an up-regulation of central nervous system (CNS) cytokine production. Central actions of proinflammatory cytokines, in particular IL-1β, are pivotal for the induction of fever and fatigue. In the present study, the influence of peripheral chronic joint inflammatory disease in rheumatoid arthritis (RA) on CNS inflammation was investigated.

K/BxN serum transfer arthritis as a model of inflammatory joint pain.

In this chapter, we describe the usage of this rheumatoid arthritis model to investigate pain-like behavior in mice, including the assessment of clinical changes and the time-dependent changes in nociceptive behavior during disease progresses.

Spinal TLR4 mediates the transition to a persistent mechanical hypersensitivity after the resolution of inflammation in serum-transferred arthritis.

Persistent pain after resolution of clinically appreciable signs of arthritis poses a therapeutic challenge, and immunosuppressive therapies do not meet this medical need. To investigate this conversion to persistent pain, we utilized the K/BxN serum transfer arthritis model, which has persistent mechanical hypersensitivity despite the resolution of visible inflammation. Toll-like receptor (TLR) 4 has been implicated as a potential therapeutic target in neuropathic and other pain models.

Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that affects approximately 1% of the population. Synovial inflammation cannot fully explain the level of pain reported by patients and facilitation of pain processing at the spinal level has been implicated. We characterized the K/BxN serum transfer arthritis model as a model of joint inflammation-induced pain and examined pharmacologic responsiveness and spinal glia activation.

Parathyroid hormone stimulates expression of the Notch ligand Jagged1 in osteoblastic cells.

We previously demonstrated that activation of the Parathyroid Hormone Receptor (PTH1R) in osteoblastic cells increases the Notch ligand Jagged1 and expands hematopoietic stem cells (HSC) through Notch signaling. However, regulation of Jagged1 by PTH in osteoblasts is poorly understood. The present study demonstrates that PTH treatment increases Jagged1 levels in a subpopulation of osteoblastic cells in vivo and in UMR106 osteoblastic cells in vitro.