Abstract
This issue of International Reviews of Immunology hosts a recurring special topic focused on T17 cells. The authors discuss the biology of this cell subset, its regulation and plasticity, along with its pivotal role in the immune defense against fungi. In addition, they address the several ways T17 cells are involved with processes such as tissue remodeling, and disease conditions such as inflammation.
T17 cells evolved as master regulators of defense responses against certain pathogens, and have been involved with tissue inflammation. Both T helper 17 (Th17) and T cytotoxic 17 (Tc17) cells have the capability to generate IL-17 and orchestrate inflammatory reactions. The IL-17 cytokine family includes six cytokines (IL-17A to IL-17F) and at least five receptors (IL-17RA to IL-17RE). Retinoic acid receptor-related orphan receptor (ROR)γt has been identified as the key transcription factor (TF) required for the Th17 cell lineage commitment. However, there is an established consensus that TFs never function alone.
In the first review of this special issue, Gao et al. discuss the newest information that sheds light on how RORγt works in concert with other TF to mediate Th17 lineage differentiation. In a second review, Tian et al. discuss the mechanisms responsible for RORγt activation that span various signaling pathways and excitingly, epigenetic regulation. These advances could allow rational design of novel therapeutics for certain inflammatory diseases, including epigenetic modulators. Nevertheless, more must be done to elucidate the exact molecular mechanisms of RORγt activation and control.
A key function of T17 cells is anti-fungal defense. Soltész et al. discuss the role of Th17 in the response against Candida and the consequence of various gene defects that impairs this cell population. The discovery of germ line mutations that affect Th17 cell differentiation and activity, involving (STAT)-3, STAT1, IL-12Rβ1 and IL-12p40, and caspase recruitment domain 9, linked this cell subset with chronic mucocutaneous candidiasis. The authors discuss evidence that connects other genetic defects with inflammatory syndromes through abnormal IL-17 / IL-17 receptor interaction or other aspects of the T17 biology.
Liang et al. focus on a specific subset of T17 cells, the Tc17 cells that express CD8 and recognize target peptides in a class I-restricted fashion. The authors discuss evidence supporting the role of Tc17 cells in infection, cancer and autoimmunity, in both man and mouse. In addition to the pathways and mechanisms involved in the differentiation of Tc17 cells, the authors discuss the effector mechanisms such as cytokines and other functions of this cell population including its functional plasticity. The origin of this cell subset is being discussed, emphasizing the key role of umbilical cord cells.
At last but not least, Liu et al. present the role of Th17 cells and other interleukin 17-producing cells in bone resorption and remodeling. This is an area of significant interest and investigation, as it has potential translational value. Nevertheless, the complexity of the biological system responsible for bone formation and remodeling is daunting as there are many categories of cells involved. One of the most exciting advances was the discovery of how T17 cells control the process of bone resorption. The authors summarize how Th17 cells mediate this effect, mainly through IL-17 which is known to orchestrate osteoclast differentiation and activation, acting on osteoclast precursors to induce RANK expression.
Altogether, much progress during the recent years highlighted the multi-faceted role of IL-17 producing cells, responsible for anti-fungal immune defense, and at the interface with a diverse range of conditions from tissue repair to inflammation and cancer, respectively.
Declaration of Interest
The author reports no conflict of interest. The authors alone are responsible for the content and writing of the article.