A Narrative Review on the Viability of Osteopathic Manipulative Medicine in Treating Irritable Bowel Syndrome With Constipation (IBS-C).

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain and alterations in bowel habits, with global prevalence. The etiology of the disease is likely multifactorial; however, autonomic nervous system (ANS) dysfunction and immune-mediated inflammation may contribute the most to the hallmark symptoms of abdominal pain and altered motility of the gut. Current pharmacological therapies operate to modulate intestinal transit, alter the composition of the gut flora and control pain.

Implications of microgravity-induced cell signaling alterations upon cancer cell growth, invasiveness, metastatic potential, and control by host immunity.

The human endeavor to venture beyond the orbit of Earth is challenged by both continuous space radiation and microgravity-induced immune dysfunction. If cancers were to develop in astronauts, it is unclear how these abnormal cells would grow and progress in the microgravity environment. It is unknown if the astronaut's immune response would be able to control or eradicate cancer.

Model Systems for the Study of Malignant Melanoma.

Since the first resection of melanoma by Hunter in 1787, efforts to treat patients with this deadly malignancy have been ongoing. Initial work to understand melanoma biology for therapeutics development began with the employment of isolated cancer cells grown in cell cultures. However, these models lack in vivo interactions with the tumor microenvironment.

Simulated microgravity-mediated reversion of murine lymphoma immune evasion.

No human has returned to the moon since the end of the Apollo program 47 years ago, however, new missions are planned for an orbital outpost. Space radiation and the potential for cancer remain as important issues to the future of human space exploration. While improved shield technologies and protective biologicals are under development, little is known concerning the interaction between cancer cells and host immunity in microgravity.

Prolonged exposure to simulated microgravity diminishes dendritic cell immunogenicity.

Immune dysfunction due to microgravity remains a hurdle in the next step of human space exploration. Dendritic cells (DC) represent a critical component of immunity, given their role in the detection of invaders and the subsequent task of activating T cells to respond and eliminate the threat. Upon encounter with microbes, DC undergo a process of maturation, whereby the cells upregulate the expression of surface proteins and secrete cytokines, both required for the optimal activation of CD4 and CD8 T cells.

T cell resistance to activation by dendritic cells requires long-term culture in simulated microgravity.

Immune impairment mediated by microgravity threatens the success of space exploration requiring long-duration spaceflight. The cells of most concern, T lymphocytes, coordinate the host response against microbial and cancerous challenges leading to elimination and long-term protection. T cells are activated upon recognition of specific microbial peptides bound on the surface of antigen presenting cells, such as dendritic cells (DC).

Ebola virus secreted glycoprotein decreases the anti-viral immunity of macrophages in early inflammatory responses.

During Ebola virus (EBOV) infection, secreted glycoprotein (sGP) is found in large quantities in the serum of both patients and infected animal models. It is thought to serve as a decoy for anti-EBOV antibodies. Using an in vitro model incorporating treatment of non-infected human THP-1 macrophages with recombinant EBOV sGP, this study sought to examine the impact of sGP upon key macrophage functions.

Differential Expression of Homing Receptor Ligands on Tumor-Associated Vasculature that Control CD8 Effector T-cell Entry.

Although CD8 T cells are critical for controlling tumors, how they are recruited and home to primary and metastatic lesions is incompletely understood. We characterized the homing receptor (HR) ligands on tumor vasculature to determine what drives their expression and their role in T-cell entry. The anatomic location of B16-OVA tumors affected the expression of E-selectin, MadCAM-1, and VCAM-1, whereas the HR ligands CXCL9 and ICAM-1 were expressed on the vasculature regardless of location.

Use of the anti-inflammatory cytokine interleukin-11 to reverse HIV-1gp120 repression of a natural killer cell line.

Enhancing natural killer (NK) cell activation has been associated with protection from human immunodeficiency virus-1 (HIV-1) infections and slowed onset of immunodeficiency. However, soluble HIV-1 envelope protein, gp120, has been shown to impair NK cell cytokine secretion and cell-mediated cytotoxicity. Here we show that gp120 suppressed IFN-γ production and cytotoxic function of a human NK cell line NK-92MI.

Mechanisms of spatial and temporal development of autoimmune vitiligo in tyrosinase-specific TCR transgenic mice.

Generalized vitiligo is thought to have an autoimmune etiology and has been correlated with the presence of CD8 T cells specific for melanocyte differentiation Ag. However, limited animal models for the disease have hampered its understanding. Thus, we generated TCR transgenic mice that recognize an epitope of the melanocyte protein, tyrosinase.

Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production.

The role of Th17 cells in type I diabetes (TID) remains largely unknown. Glutamic acid decarboxylase (GAD) sequence 206-220 (designated GAD2) represents a late-stage epitope, but GAD2-specific T cell receptor transgenic T cells producing interferon gamma (IFNgamma) protect against passive TID. Because IFNgamma is known to inhibit Th17 cells, effective presentation of GAD2 peptide under noninflammatory conditions may protect against TID at advanced disease stages.

NKT cell activation mediates neutrophil IFN-gamma production and renal ischemia-reperfusion injury.

Previous work has shown that ischemia-reperfusion (IR) injury (IRI) is dependent on CD4(+) T cells from naive mice acting within 24 h. We hypothesize that NKT cells are key participants in the early innate response in IRI. Kidneys from C57BL/6 mice were subjected to IRI (0.

Specific T regulatory cells display broad suppressive functions against experimental allergic encephalomyelitis upon activation with cognate antigen.

To date, very few Ag-based regimens have been defined that could expand T regulatory (Treg) cells to reverse autoimmunity. Additional understanding of Treg function with respect to specificity and broad suppression should help overcome these limitations. Ig-proteolipid protein (PLP)1, an Ig carrying a PLP1 peptide corresponding to amino acid residues 139-151 of PLP, displayed potent tolerogenic functions and proved effective against experimental allergic encephalomyelitis (EAE).

IL-10 diminishes CTLA-4 expression on islet-resident T cells and sustains their activation rather than tolerance.

IL-10, a powerful anti-Th1 cytokine, has shown paradoxical effects against diabetes. The mechanism underlying such variable function remains largely undefined. An approach for controlled mobilization of endogenous IL-10 was applied to the NOD mouse and indicated that IL-10 encounter with diabetogenic T cells within the islets sustains activation, while encounter occurring peripheral to the islets induces tolerance.

A sudden decline in active membrane-bound TGF-beta impairs both T regulatory cell function and protection against autoimmune diabetes.

Autoimmunity presumably manifests as a consequence of a shortfall in the maintenance of peripheral tolerance by CD4(+)CD25(+) T regulatory cells (Tregs). However, the mechanism underlying the functional impairment of Tregs remains largely undefined. In this study a glutamic acid decarboxylase (GAD) diabetogenic epitope was expressed on an Ig to enhance tolerogenic function, and the resulting Ig-GAD expanded Tregs in both young and older insulitis-positive, nonobese diabetic (NOD) mice, but delayed autoimmune diabetes only in the former.

IL-4 utilizes an alternative receptor to drive apoptosis of Th1 cells and skews neonatal immunity toward Th2.

Primary neonatal Th1 cells develop alongside of Th2 upon priming of the newborn but undergo apoptosis upon recall with antigen. These Th1 cells were isolated, and their death was correlated with elevated IL-13Ralpha1 chain expression. Strikingly, neutralization of Th2s' IL-4 reduced apoptosis, sustained recall responses, and the live Th1 cells displayed a decrease in IL-13Ralpha1 expression.

Break of neonatal Th1 tolerance and exacerbation of experimental allergic encephalomyelitis by interference with B7 costimulation.

Ig-PLP1 is an Ig chimera expressing proteolipid protein-1 (PLP1) peptide corresponding to aa residues 139-151 of PLP. Newborn mice given Ig-PLP1 in saline on the day of birth and challenged 7 wk later with PLP1 peptide in CFA develop an organ-specific neonatal immunity that confers resistance against experimental allergic encephalomyelitis. The T cell responses in these animals comprise Th2 cells in the lymph node and anergic Th1 lymphocytes in the spleen.

On the role of dendritic cells in peripheral T cell tolerance and modulation of autoimmunity.

Recently, it has become clear that dendritic cells (DCs) are essential for the priming of T cell responses. However, their role in the maintenance of peripheral T cell tolerance remains largely undefined. Herein, an antigen-presenting cell (APC) transfer system was devised and applied to experimental allergic encephalomyelitis (EAE), to evaluate the contribution that DCs play in peripheral T cell tolerance.