For many years, the aryl hydrocarbon receptor (AhR) was studied for its role in toxicity and carcinogenicity. Indeed, for decades, toxicologists could only speculate about the “normal physiological” role for the AhR. The only ligand-activated member of the PER/ARNT/SIM family of transcription factors was known only for its promiscuous binding to and activation by a variety of environmental chemicals including halogenated (e.g., 2,3,7,8 tetrachlorodibenzo-p-dioxin/TCDD; ortho-PCBs) and non-halogenated (benzo(a)pyrene; chrysene) hydrocarbons. In recent years, however, it has become clear that the AhR-driven outcomes studied previously were only a harbinger of the many contributions that the AhR makes to normal and pathologic physiology in the absence of environmental ligands. Specifically, accumulating evidence indicates that the AhR controls the development of regulatory T cells (Tregs) and M2-like tumor-associated macrophages, both of which have been closely associated with tumor growth and poor cancer prognoses. Conversely, lack of sufficient AhR activation in Tregs or antigen-presenting cells and AhR activation in Th17 cells has been associated with autoimmunity and inflammation.
Here, we aim to present a cluster of related manuscripts on the important role of the AhR in regulating innate and adaptive immunity with an emphasis on autoimmunity and immunosuppression in the context of cancer. For this Research Topic, we are seeking original research articles, mini-reviews, perspectives, or opinion/commentary articles covering the following sub-topics:
1. Seminal findings in immunotoxicology that led to an understanding of the AhR in human disease
2. Factors that regulate AhR expression, modify its activity, and mediate its effect on immune cells
3. The AhR as an immune checkpoint in cancer
4. The AhR as a key modulator of autoimmunity
5. The potential for AhR modulators as immunotherapeutics in cancer and autoimmunity
Topic Editor David Sherr is founder and Chief Scientific Officer of company Hercules Pharmaceuticals, Inc. which licenses AHR inhibitors. Topic Editor Francisco Quintana is co-founder of AntolRx, which develops therapies for autoimmune diseases. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
For many years, the aryl hydrocarbon receptor (AhR) was studied for its role in toxicity and carcinogenicity. Indeed, for decades, toxicologists could only speculate about the “normal physiological” role for the AhR. The only ligand-activated member of the PER/ARNT/SIM family of transcription factors was known only for its promiscuous binding to and activation by a variety of environmental chemicals including halogenated (e.g., 2,3,7,8 tetrachlorodibenzo-p-dioxin/TCDD; ortho-PCBs) and non-halogenated (benzo(a)pyrene; chrysene) hydrocarbons. In recent years, however, it has become clear that the AhR-driven outcomes studied previously were only a harbinger of the many contributions that the AhR makes to normal and pathologic physiology in the absence of environmental ligands. Specifically, accumulating evidence indicates that the AhR controls the development of regulatory T cells (Tregs) and M2-like tumor-associated macrophages, both of which have been closely associated with tumor growth and poor cancer prognoses. Conversely, lack of sufficient AhR activation in Tregs or antigen-presenting cells and AhR activation in Th17 cells has been associated with autoimmunity and inflammation.
Here, we aim to present a cluster of related manuscripts on the important role of the AhR in regulating innate and adaptive immunity with an emphasis on autoimmunity and immunosuppression in the context of cancer. For this Research Topic, we are seeking original research articles, mini-reviews, perspectives, or opinion/commentary articles covering the following sub-topics:
1. Seminal findings in immunotoxicology that led to an understanding of the AhR in human disease
2. Factors that regulate AhR expression, modify its activity, and mediate its effect on immune cells
3. The AhR as an immune checkpoint in cancer
4. The AhR as a key modulator of autoimmunity
5. The potential for AhR modulators as immunotherapeutics in cancer and autoimmunity
Topic Editor David Sherr is founder and Chief Scientific Officer of company Hercules Pharmaceuticals, Inc. which licenses AHR inhibitors. Topic Editor Francisco Quintana is co-founder of AntolRx, which develops therapies for autoimmune diseases. All other Topic Editors declare no competing interests with regards to the Research Topic subject.