**3.1 T helper 17 subset (Th17)**

There are specific cytokines which are important for the differentiation of naïve T cells into the T helper 17 subset. IL-6 and TGF-β together are important for the development of this population [31]. The blockade of IL-6 through anti-IL-6 antibody was found to inhibit the development of Th17 cells [32]. Furthermore, the addition of IL-1β to culture medium was reported to enhance the development of the Th17 subset. IL-1 receptor knockout mice showed a significant defect in the Th17 population [33]. IL-1β was found to enhance expression of the transcription factors orphan nuclear receptor (ROR-γt) and interferon regulatory factor-4 (IRF-4), which are responsible for the development of the Th17 subset [34]. The Th17 subset could secrete a variety of cytokines including IL-17A, IL-17F, IL-21, and IL-22, which have a pathogenic effect in certain autoimmune mouse models [35].

**155**

CD4+

*Role of Aryl Hydrocarbon-Ligands in the Regulation of Autoimmunity*

Moreover, IL-23 which is secreted by antigen-presenting cells (APCs) after pathogen recognition is important for the maintenance of the Th17 population [31]. These data suggested that the Th17 subset is a very sensitive subset requiring specific

The presence of IL-10 and TGF-β was reported to skew the development of naïve T cell toward the development of T regulatory cells (Treg) [36]. The main function of Treg is to suppress the immune response, and to inhibit the production of pro-inflammatory cytokines such as IL-2 and IFN-γ. The development of this population could be inhibited in the presence of IL-1β and IL-6 [37]. Treg cells are characterized by the expression of CD25 and the forkhead box p3 (Foxp3) transcription factor [38]. The decreased production of pro-inflammatory cytokines such as IL-6 and IL-1β could help in skewing the differentiation of naïve T cells

In some cases, the immune system attacks our own tissues, causing autoimmunity. IL-17-producing cells play important roles in the development of different autoimmune diseases including rheumatoid arthritis (RA), an inflammation disorder which attacks the synovial joints and multiple sclerosis (MS), characterized by inflammation of the myelin sheath, resulting in de-myelination. It was reported that IL-17-knockout mice were protected against these autoimmune diseases [39]. In contrast, a high level of IL-17 was detected in the serum of patients with MS, RA, and systemic lupus erythematous (SLE). This suggests that Th17 cells expressing high levels of ROR-γt and IL-23R could be one of the causes of these diseases [40]. In addition, it was also reported that the Th17 subset increases the severity of EAE,

**5. Effects of AhR-ligands on the production of Th17/Treg subsets and** 

Differentiation of Th17 cells depends on the presence of interleukin (IL)-6 and transforming growth factor (TGF)-beta, and it could be regulated by the activation of AhR [43]. The differentiation of Th17 cells could be enhanced by endogenous AhR agonists found normally in culture medium. The RPMI culture medium could support very low levels of Th17 polarization, because it lacks the presence of these ligands. In contrast, Iscove's modified Dulbecco's medium (IMDM) is known to be rich in aromatic amino acids, such as tryptophan, histidine, and phenylalanine, that were thought to be the precursors of endogenous AhR-ligands and therefore significantly increase the development of Th17 cells [43]. In addition, treating naïve

T cells with the AhR-ligand FICZ in Th17 cell polarizing conditions helps in

of the Th17 population, and as a result, significant amounts of IL-17*a*, IL-17*f,* and IL-22 cytokines will be secreted. In contrast, a significant reduction in the development of Th17 cells was observed in AhR knockout mice, suggesting that the devel-

The activation of AhR with different AhR-ligands can regulate Treg/Th17 balance in mice. A significant increase in Treg population was noticed when AhR

T cells, *in vitro*, toward the development

*DOI: http://dx.doi.org/10.5772/intechopen.80840*

cytokines for development and maintenance.

toward the development of the Treg subset.

**4. Role of Th17 in autoimmunity**

diabetes, and RA [41, 42].

**autoimmunity**

skewing the differentiation of naive CD4+

opment of the Th17 cells was AhR dependent [35].

**3.2 T regulatory subset (Treg)**

Moreover, IL-23 which is secreted by antigen-presenting cells (APCs) after pathogen recognition is important for the maintenance of the Th17 population [31]. These data suggested that the Th17 subset is a very sensitive subset requiring specific cytokines for development and maintenance.
