Macrophage-dendritic cell regulation

NF-kB regulates both innate and adaptive immune responses ( immune defense) [2]. Understanding the function of NF-kB in the development, maintenance, and activation of cells from the immune system (including hematopoietic cells, macrophages, dendritic cells, B and T lymphocytes) has greatly benefited from the analysis of knockout mice in which individual NF-kB family members were defective. 

Macrophage dendritic cell interaction in the regulation of the IgE response in asthma. Clinical and Experimental Allergy, 23, 4-6. 

IL-18 also induces IL-4, IL-10 and IL-13 production, increases IgE expression on B cells and in association with IL-2, it enhances stimulus-induced IL-4 production from TH2 cells. Bone marrow-derived basophils produce IL-4 and IL-13 in response to a stimulus from IL-18 and IL-3. IL-18 in combination with IL-12 induces IFN-y from dendritic cells and bone marrow-derived macrophages. Adhesion molecules, ICAM-1 and VCAM-1, are induced by this cytokine on synovial fibroblasts and endothelial cells. It inhibits osteoclast formation via its induction of GM-CSF from T cells. The receptors ofIL-18, IL-18Ra and IL-18R(3, share their signaling mechanisms via the IL-1R family. Toll-like receptors also share the downstream signaling pathway of IL-18 and are known to regulate IL-18 expression. 

FceRII (CD23) receptor plays an important role in regulation of IgE synthesis. In comparison to FceRI, it shows low affinity to IgE. It is found on dendritic cells, macrophages, monocytes, platelets, T and B lymphocytes, and eosinophils. In its soluble form, it sometimes activates B lymphocytes to produce IgE. 

Immune responses can be divided into type 1 and type 2, based on the pattern of cytokine secretion and functional outcome of the immune response. Type 1 immune responses are characterized by secretion of IFN-gamma, production of IgG2a in mice, and activation of macrophages, NK cells, and cytotoxic T-cells. Type 2 responses are characterized by secretion of IL-4, IL-5, and IL-13 and by IgGl and IgE production. The responses are reciprocally regulated. How the polarization of the immune response toward type 1 or type 2 is determined is not exactly understood. IL-12 is an important factor that drives the type 1 response, and IL-4 is implicated in the type 2 response. Microbial products such as LPS and bacterial DNA stimulate the secretion of IL-12 by dendritic cells and preferentially induce type 1 immune responses. 

Holt, P.G., Schon-Hegrad, M.A. and Oliver, J. (1988). MHC class II antigen-bearing dendritic cells in pulmonary tissues of the rat. Regulation of antigen presentation activity by endogenous macrophage populations. J. Exp. Med. 167, 262-274. 

Shared receptors are defined as able to bind more than one CK this concept is only valid inside each CK family. For example CCL20, alternatively named liver and activation-regulated CK (LARC), macrophage inflammatory protein-da (MIP-3a) or Exodus-1, is the only CK known to interact with CC CK receptor 6 (CCR6), a property shared with the antimicrobial (i-defensins. The ligand-receptor pair CCL20-CCR6 is responsible for the chemoattraction of immature dendritic cells, effector/memory T cells, and B cells and plays a role at skin and mucosal surfaces under homeostatic and... 

If cytokines are themselves instrumental in regulating the development of differentiated Th-cell populations, then an intriguing question arises as to the provenance of these cytokines before a mature immune response has evolved. In the case of Thl-cell development then presumably the stimulation by dendritic cell- and/or macrophage-derived IL-12 of IFN-y production by NK cells and the concerted action of IL-12 and IFN-yon Thl-cell precursors may provide one answer. One suggestion regarding the evolution of Th2-cell... 

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