Page 636 - Veterinary Immunology, 10th Edition

Regulatory Macrophages
VetBooks.ir Cytokines cause macrophage polarization. Thus exposure to IFN-γ

generates classically activated M1 cells. Exposure of macrophages

to IL-4 or IL-13, in contrast, results in the development of M2 cells
(Chapter 18). M2 cells participate in tolerance induction, suppress
inflammation, and participate in tissue repair. M2 cells increase
expression of the macrophage mannose receptor, the β-glucan

receptor, and CD163; enhance endocytosis and antigen processing;
and increase MHC class II expression. M2 macrophages produce
large amounts of the Th2 and regulatory cytokines such as IL-4, IL-
13, IL-10, TGF-β, and IL-1RA. They are not killer cells because they

produce arginase, which generates ornithine rather than nitric
oxide (see Fig. 6.7).
In healthy animals, M2 polarized cells may be found in the
placenta and lung, where they inhibit dendritic cell antigen

presentation and mitogen responses in lymphocytes. M2
macrophages are responsible for control of granuloma formation as
well as for skin immune tolerance induced by ultraviolet B
radiation. They can also be found in healing tissues, where they are

associated with angiogenesis.

Indoleamine 2,3-Dioxygenase and Tolerance

Many regulatory cells, including Tregs, dendritic cells, some
macrophages, fibroblasts, trophoblast giant cells, endothelial cells,

and some tumor cell lines, produce indoleamine 2,3-dioxygenase
(IDO). This enzyme catalyzes the oxidative degradation of the
amino acid tryptophan, resulting in its local depletion. Tryptophan
is required for the mTOR pathway in T cells so that they undergo
cell cycle arrest and apoptosis when deprived of tryptophan. IDO

therefore inhibits T cell activation, proliferation, and survival and
promotes peripheral tolerance. Th1 cells appear to be more
sensitive to tryptophan depletion than are Th2 cells. Treg cells may

also induce IDO expression in some dendritic cells. IDO activity has
also been documented in T cell tolerance to tumors, as a negative
regulator in autoimmune diseases, and in some allergies. IDO plays
a key role in preventing immunological rejection of the fetus and of
liver and corneal allografts (Chapter 34). IDO may also act as a

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