Page 672 - Veterinary Immunology, 10th Edition

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Intestinal Treg cells are a subset of CD4 Th cells required to
VetBooks.ir maintain the body's commensal relationship with its microbiota.
Treg cells produce IL-10 as well as expressing high levels of CTLA-
4 (cytotoxic T lymphocyte antigen 4), the inhibitory ligand for

CD80. Treg production occurs in response to signals from both the
microbiota and enterocytes. These Treg cells, when acted on by
proinflammatory cytokines, can convert to IL-17 or IFN-γ -
expressing effectors and so “break tolerance.” Under these

circumstances, Th17 cells can give rise to IFN-γ producers that
functionally resemble Th1 cells, and it is likely that many intestinal
Th1 cells develop through this pathway. Under other circumstances
the Treg cells may convert to helper cells and promote the switch to

IgA production. Indeed, about 75% of the IgA reactive to the
microbiota is produced through a T-dependent pathway controlled
by Treg cells.
Mucosal inflammation is therefore actively suppressed by the

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production of large numbers of IL-10-producing FoxP3 Tregs.
Under stable conditions, the production of Treg cells is favored
while that of Th17 cells is suppressed. In the absence of Treg cells,
uncontrolled effector T cells will respond to microbial antigens and

trigger inflammatory bowel disease. Likewise, IL-10 deficient mice
develop chronic unremitting colitis driven by IL-23 and the Th17
pathway.
It is also clear, however, that this tolerance can only go so far.

Should a potential pathogen seek to invade the body from the
intestine, then the immune system must be prepared to act
aggressively to prevent this. This is mediated by proinflammatory
Th17 cells.

Th17 cells.

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As described in Chapter 20, Th17 cells are a subset of CD4 T cells
that regulate inflammation and maintain the intestinal epithelial
barrier. Under the influence of IL-23, they produce the
proinflammatory cytokines IL-17A, IL-17F, and IL-22. They also

produce the antibacterial cytokine IL-26 (Fig. 21.10). Like Treg cells,
the development of Th17 cells is regulated by signals from the
microbiota and from enterocytes. Th17 cell development is

specifically stimulated by the attachment of SFBs to enterocytes.

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