The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cel...The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model： we cultured hematomas forming during an osteotomy （artificial bone fracture） of the femur during total hip arthroplasty （THA） in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells （i.e., neutrophils）. Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma.展开更多
In a recent issue of Immunity,Kim et al.reported previously unknown effects of glucocorticoids on murine regulatory T(Treg)cells,and this report added another very interesting perspective to the already very diverse b...In a recent issue of Immunity,Kim et al.reported previously unknown effects of glucocorticoids on murine regulatory T(Treg)cells,and this report added another very interesting perspective to the already very diverse body of knowledge about these important hormones and therapeutics compared to the body of knowledge about other clinically used drugs.1 Treg cells are important regulators of the immune response in autoimmune and allergic inflammation.展开更多
In a recent issue of Nature Immunology,Chen et al.identified differential expression signatures of metabolic programs within the germinal center(GC)compartment to distinguish GC B cells from different zones[1].Further...In a recent issue of Nature Immunology,Chen et al.identified differential expression signatures of metabolic programs within the germinal center(GC)compartment to distinguish GC B cells from different zones[1].Furthermore,they identified an important role of oxidative phosphorylation(OXPHOS)in the process of positive selection of B cells with higher-affinity B cell receptors(BCRs)in GCs.GCs are inducible secondary lymphoid microanatomical structures that provide niches for B cells to capture and present antigens in the light zone(LZ)and to undergo clonal expansion and BCR somatic hypermutation(SHM)in the dark zone(DZ)Fig.1.Alternating migration of activated GC B cells between the LZ and DZ is assumed to result in positive selection of clones with higher-affinity B cell antigen receptors.These clones are characterized by accelerated cell division,suggesting a genomic program activated by BCR and CD40 signaling[2].展开更多
文摘The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model： we cultured hematomas forming during an osteotomy （artificial bone fracture） of the femur during total hip arthroplasty （THA） in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells （i.e., neutrophils）. Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma.
基金Open Access funding enabled and organized by Projekt DEAL。
文摘In a recent issue of Immunity,Kim et al.reported previously unknown effects of glucocorticoids on murine regulatory T(Treg)cells,and this report added another very interesting perspective to the already very diverse body of knowledge about these important hormones and therapeutics compared to the body of knowledge about other clinically used drugs.1 Treg cells are important regulators of the immune response in autoimmune and allergic inflammation.
基金Open Access funding enabled and organized by Projekt DEAL.
文摘In a recent issue of Nature Immunology,Chen et al.identified differential expression signatures of metabolic programs within the germinal center(GC)compartment to distinguish GC B cells from different zones[1].Furthermore,they identified an important role of oxidative phosphorylation(OXPHOS)in the process of positive selection of B cells with higher-affinity B cell receptors(BCRs)in GCs.GCs are inducible secondary lymphoid microanatomical structures that provide niches for B cells to capture and present antigens in the light zone(LZ)and to undergo clonal expansion and BCR somatic hypermutation(SHM)in the dark zone(DZ)Fig.1.Alternating migration of activated GC B cells between the LZ and DZ is assumed to result in positive selection of clones with higher-affinity B cell antigen receptors.These clones are characterized by accelerated cell division,suggesting a genomic program activated by BCR and CD40 signaling[2].
