The Emerging World of Microbiome in Autoimmune Disorders: Opportunities and Challenges.

Trillions of commensal bacteria colonizing humans (microbiome) have emerged as essential player(s) in human health. The alteration of the same has been linked with diseases including autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Gut bacteria are separated from the host through a physical barrier such as skin or gut epithelial lining.

Lupus-Associated Pulmonary Arterial Hypertension: Variable Course and Importance of Prompt Recognition.

We describe a critically ill young woman with systemic lupus erythematosus (SLE) presenting with circulatory shock, multiorgan dysfunction, and elevated right-sided heart pressures. She was found to have recurrent acute severe pulmonary arterial hypertension (PAH) in the setting of an SLE flare. Our report highlights the variable course that SLE-associated PAH can take in the same patient and the implications of this for instituting the most effective treatment approach with each episode.

Successful use of Rituximab in a patient with recalcitrant multisystemic eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare eosinophil-rich disorder characterised by necrotising granulomatous inflammation affecting small to medium sized vessels. Extrapulmonary manifestations can be life-threatening when heart, central nervous system (CNS), gastrointestinal tract or kidneys are affected. We describe a case of a 56-year-old woman with a long-standing history of asthma, who presented with an acute sudden painless loss of vision after she had been recently diagnosed with EGPA and induced with pulse steroids and cyclophosphamide.

Effects of the physico-chemical nature of two biomimetic crystals on the innate immune response.

The influence of the physico-chemical features of particulates made of calcium phosphate (hydroxyapatite, HAP) crystals, or monosodium urate monohydrate (MSUM) crystals, on the innate immune response was investigated in mice after intraperitoneal injections. The phenotype and activation status of harvested peritoneal cells from C57BL/6 mice was determined by flow cytometry analysis at 24, 48 and 72 h after particulate injections and compared to a known adjuvant, aluminum phosphate (ALP). A rigorous characterization of the chemistry, structure, morphology and particle size of the particulates was completed.

Effects of LPS-mediated bystander activation in the innate immune system.

LPS induces dendritic cell (DC) activation, but the precise in vivo mechanism is unclear since DCs express low levels of TLR4. Here, it is shown that DCs can be activated in response to LPS through a bystander mechanism. This result was obtained using chimeric mice reconstituted with LPS-responsive and nonresponsive bone marrow cells.

IL-18 bridges innate and adaptive immunity through IFN-gamma and the CD134 pathway.

IL-18 induces inflammation resulting in either enhanced protection from pathogens or exacerbation of autoimmunity, and T cells are profoundly activated during these responses. How IL-18 influences T cell activation is unknown, but this study in mice shows that IL-18 boosted Ag-specific T cell clonal expansion of effector T cells and induced a subpopulation of IFN-gamma superproducing T cells. Commitment to IFN-gamma production through IL-18 was independent of NK cells and IL-12 but dependent on host-derived IFN-gamma.

CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches.

T cell activation by dendritic cells (DCs) is critical to the initiation of adaptive immune responses and protection against pathogens. Here, we demonstrate that a specialized DC subset in Peyer's patches (PPs) mediates the rapid activation of pathogen specific T cells. This DC subset is characterized by the expression of the chemokine receptor CCR6 and is found only in PPs.

Duration of alloantigen presentation and avidity of T cell antigen recognition correlate with immunodominance of CTL response to minor histocompatibility antigens.

CD8 T lymphocytes (CTL) responsive to immunodominant minor histocompatibility (minor H) Ags are thought to play a disproportionate role in allograft rejection in MHC-identical solid and bone marrow transplant settings. Although many studies have addressed the mechanisms underlying immunodominance in models of infectious diseases, cancer immunotherapy, and allograft immunity, key issues regarding the molecular basis of immunodominance remain poorly understood. In this study, we exploit the minor H Ag system to understand the relationship of the various biochemical parameters of Ag presentation and recognition to immunodominance.

The H4b minor histocompatibility antigen is caused by a combination of genetically determined and posttranslational modifications.

Minor histocompatibility (H) Ag disparities result in graft-vs-host disease and chronic solid allograft rejection in MHC-identical donor-recipient combinations. Minor H Ags are self protein-derived peptides presented by MHC class I molecules. Most arise as a consequence of allelic variation in the bound peptide (p) that results in TCR recognizing the p/MHC as foreign.

Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor.

Prostaglandin E(2) (PGE(2)), a major COX metabolite, plays important roles in several facets of tumor biology. We characterized the contribution of the PGE(2) EP2 receptor to cancer-associated immune deficiency using EP2(-/-) mice. EP2(-/-) mice exhibited significantly attenuated tumor growth and longer survival times when challenged with MC26 or Lewis lung carcinoma cell lines as compared with their wild-type littermates.

Cutting edge: the minor histocompatibility antigen H60 peptide interacts with both H-2Kb and NKG2D.

Minor histocompatibility Ags elicit cell-mediated immune responses and graft rejection in individuals receiving MHC-matched tissues. H60 represents a dominant Ag that elicits a strong CTL response in C57BL/6 mice immunized against BALB.B.