scholarly journals Faculty Opinions recommendation of Regulation of innate lymphoid cells by aryl hydrocarbon receptor.

Author(s):  
Joerg Lehmann
Immunity ◽  
2012 ◽  
Vol 36 (1) ◽  
pp. 92-104 ◽  
Author(s):  
Ju Qiu ◽  
Jennifer J. Heller ◽  
Xiaohuan Guo ◽  
Zong-ming E. Chen ◽  
Kamonwan Fish ◽  
...  

2020 ◽  
Vol 6 (3) ◽  
pp. eaay8230 ◽  
Author(s):  
Jiaxuan Chen ◽  
Carolyn A. Haller ◽  
Finith E. Jernigan ◽  
Steffi K. Koerner ◽  
Daniel J. Wong ◽  
...  

Aryl hydrocarbon receptor (AHR) is an essential regulator of gut immunity and a promising therapeutic target for inflammatory bowel disease (IBD). Current AHR agonists are inadequate for clinical translation due to low activity, inadequate pharmacokinetics, or toxicity. We synthesized a structurally diverse library and used integrated computational and experimental studies to discover mechanisms governing ligand-receptor interaction and to design potent drug leads PY109 and PY108, which display physiochemical drug-likeness properties, desirable pharmacokinetic profiles, and low toxicity. In a murine model of dextran sulfate sodium–induced colitis, orally administered compounds increase interleukin-22 (IL-22) production and accelerate mucosal healing by modulating mucosal adaptive and innate lymphoid cells. AHR and IL-22 pathway induction was confirmed using RNA sequencing and characterization of the lymphocyte protein-protein interaction network. Significant induction of IL-22 was also observed using human T cells from patients with IBD. Our findings support rationally designed AHR agonists for IBD therapy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Alba De Juan ◽  
Elodie Segura

Accumulating evidence indicates that nutrition can modulate the immune system through metabolites, either produced by host digestion or by microbiota metabolism. In this review, we focus on dietary metabolites that are agonists of the Aryl hydrocarbon Receptor (AhR). AhR is a ligand-activated transcription factor, initially characterized for its interaction with xenobiotic pollutants. Numerous studies have shown that AhR also recognizes indoles and tryptophan catabolites originating from dietary compounds and commensal bacteria. Here, we review recent work employing diet manipulation to address the impact of nutritional AhR agonists on immune responses, both locally in the intestine and at distant sites. In particular, we examine the physiological role of these metabolites in immune cell development and functions (including T lymphocytes, innate-like lymphoid cells, and mononuclear phagocytes) and their effect in inflammatory disorders.


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