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March 2024

Nourishing insights: diet-driven adaptation of eosinophils

Article: Nutrient-Derived Signals Regulate Eosinophil Adaptation to the Small Intestine
Kutyavin, Vassily I, et al.
National Academy of Sciences of the United States of America, vol. 121, no. 5, 25 Jan. 2024

Reviewed by Krishan Chhiba, MD, PhD, Northwestern University, Chicago, United States

Eosinophils are abundant in the small intestines of mice and humans, where nutrients are absorbed. Few studies have examined the effect of diet on eosinophils residing in the small intestine. The authors of this study use BrdU labeling to mark proliferating eosinophils. They show that eosinophils initially enter the tissues near the crypt and migrate from the crypt to the villus of the small intestine. These spatially distinct eosinophils are also noted to be transcriptionally distinct and can be distinguished by their expression of α4β7 (crypt) and CD22 (villus). The authors propose that these changes demonstrate eosinophil adaptation. IL-5, IL-33 and microbiome are not necessary for adaptation. RAR signaling antagonist reduced small intestine eosinophils and preferentially the CD22+ villus-resident eosinophils. Mice that also ate a high-protein diet exhibited an even further reduced eosinophil frequencies, suggesting that the pathways involved are distinct. Finally, the authors show that adoptively transferred of eosinophils still responded to the high-protein diet in host mice suggesting that dietary nutrients are not affecting eosinophil development in the bone marrow. 

While clinical improvement is seen with dietary modification in EGIDs, the mechanism of this effect needs further investigation. This study adds to our understanding of eosinophils by showing how the nutrient microenvironment contributes to the adaptation of eosinophils in the gastrointestinal tract. Efficacy of eosinophil-targeted therapies in EGIDs may relate to the subpopulations of eosinophils in the gastrointestinal tract that are targeted. Further studies in humans are needed.

While reviewing this paper, the following questions come to mind: (1) Are α4β7+ (crypt) and CD22+ (villus) eosinophil subtypes found in humans with EoN during active disease and how do their frequencies change after an amino acid-based elemental diet? (2) Since eosinophil apoptosis is not triggered by direct exposure to high amino acid concentration, is there an intermediary cell type that helps to orchestrate the effect shown in this manuscript? (3) What is the consequence of increased or decreased villus-resident eosinophils on tissue inflammation and disease pathology?, and (4) Will spatial transcriptomics of eosinophils in the small intestine identify even further complexity of the spatial adaptation taking place.

Krishan Chhiba, MD, PhD, is an Allergy and Immunology fellow and post-doctoral researcher at Northwestern University. He obtained his MD and PhD degrees at Northwestern, where he studied the phenotypic and functional plasticity of mast cells and mast cell-targeting therapeutics under the mentorship of Drs. Bruce Bochner and Paul Bryce. He is performing his post-doctoral research in the laboratory of Dr. Fei Li Kuang. His basic science research will focus on defining the roles of eosinophils in eosinophilic gastrointestinal disease and allergic hypersensitivity reactions. He is leveraging advances in eosinophils transcriptomics and proteomics to elucidate the changes underlying the development of peripheral eosinophilia and tissue eosinophilia in humans. Krishan is serving on the IES Scientific Program Committee.

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