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The role of the innate immune system in granulomatous disorders.

ABSTRACT: The dynamic structure of the granuloma serves to protect the body from microbiological challenge. This organized aggregate of immune cells seeks to contain this challenge and protect against dissemination, giving host immune cells a chance to eradicate the threat. A number of systemic diseases are characterized by this specialized inflammatory process and granulomas have been shown to develop at multiple body sites and in various tissues. Central to this process is the macrophage and the arms of the innate immune response. This review seeks to explore how the innate immune response drives this inflammatory process in a contrast of diseases, particularly those with a component of immunodeficiency. By understanding the genes and inflammatory mechanisms behind this specialized immune response, will guide research in the development of novel therapeutics to combat granulomatous diseases.

SUBMITTER: Petersen HJ

PROVIDER: S-EPMC3662972 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The role of the innate immune system in granulomatous disorders.

Petersen Helen J HJ Smith Andrew M AM

Frontiers in immunology 20130524

The dynamic structure of the granuloma serves to protect the body from microbiological challenge. This organized aggregate of immune cells seeks to contain this challenge and protect against dissemination, giving host immune cells a chance to eradicate the threat. A number of systemic diseases are characterized by this specialized inflammatory process and granulomas have been shown to develop at multiple body sites and in various tissues. Central to this process is the macrophage and the arms of ...[more]

PMID: 23745122

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Project description:Fibroblast growth factor-23 (FGF-23) is a bone-derived hormone that activates FGFR/?-Klotho binary complexes in the kidney renal tubules to regulate phosphate reabsorption and vitamin D metabolism. The objective of this review is to discuss the emerging data that show that FGF-23 has functions beyond regulation of mineral metabolism, including roles in innate immune and hemodynamic responses. Excess FGF-23 is associated with inflammation and adverse infectious outcomes, as well as increased morbidity and mortality, particularly in patients with chronic kidney disease. Enhancer elements in the FGF-23 promoter have been identified that mediate the effects of inflammatory cytokines to stimulate FGF-23 gene transcription in bone. In addition, inflammation induces ectopic expression of FGF-23 and ?-Klotho in macrophages that do not normally express FGF-23 or its binary receptor complexes. These observations suggest that FGF-23 may play an important role in regulating innate immunity through multiple potential mechanisms. Circulating FGF-23 acts as a counter-regulatory hormone to suppress 1,25D production in the proximal tubule of the kidney. Since vitamin D deficiency may predispose infectious and cardiovascular diseases, FGF-23 effects on innate immune responses may be due to suppression of 1,25D production. Alternatively, systemic and locally produced FGF-23 may modulate immune functions through direct interactions with myeloid cells, including macrophages and polymorphonuclear leukocytes to impair immune cell functions. Short-acting small molecules that reversibly inhibit FGF-23 offer the potential to block pro-inflammatory and cardiotoxic effects of FGF-23 with less side effects compared with FGF-23 blocking antibodies that have the potential to cause hyperphosphatemia and soft tissue calcifications in animal models. In conclusion, there are several mechanisms by which FGF-23 impacts the innate immune system and further investigation is critical for the development of therapies to treat diseases associated with elevated FGF-23.

Dataset Information

The role of the innate immune system in granulomatous disorders.

Publications

The role of the innate immune system in granulomatous disorders.

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