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October 2023

Neuromedin U programs eosinophils to promote mucosal immunity of the small intestine

Li Y, Liu S, Zhou K et al

Science 2023; Vol 381, Issue 6663 (14 September)

This review has been largely generated by Beth Jacobson, PhD with input from Marc Rothenberg, MD, PhD.

The Neuromedin U receptor 1 (NMUR) has previously described as ILC2-specific has now been found to be expressed on a subset of longer lived eosinophils specifically in the small intestine that also have features associated with degranulation, higher CD11c and MHC II, increased cholesterol biosynthesis, and less active cytokine production. Interestingly, ILC2s are not required for NMUR+ eosinophils to populate the small intestine during homeostasis. Through intrinsic pathways, these NMUR1+ eosinophils increase small intestine goblet cell differentiation in vivo and increase size of organoid cultures.  

There are several technical advances in this paper including development of (1) a novel knock-in strain to report NMUR1 as compared to previous bacterial artificial chromosome construct models; (2) a new knock-in EPX-Cre strain similar in design to Doyle, J Leukoc Biol 2013 94(1):17, yet the efficiency and expression of EPX is unknown in this strain; (3) single cell RNAseq of eosinophil populations derived from tissues using 10X Genomics post-sorting for Siglec-F+ cells; and (4) methods showing NMUR+ eosinophils can modulate intestinal organoid culture growth dynamics.

There are a number of outstanding questions such as (1) How is the intestine imprinting these NMUR+ eosinophils?; (2) What mechanism are NMUR+ eosinophils using to increase goblet cell differentiation?; and (3); Can NMUR-specific eosinophils be targeted for treatment in inflammatory intestinal disease?  Furthermore, there is a need to reinforce reporting of strain origins to keep aware of potential differences in data going forward in publications.

Chronic HDM exposure shows time-of-day and sex-based differences in inflammatory response associated with lung circadian clock disruption

Srinivasan A, Giri A, Duraisamy SK et al

iScience. 2023 Aug 9;26(9):107580. doi: 10.1016/j.isci.2023.107580. eCollection 2023 Sep 15.PMID: 37664635

Reviewed by Julia Teppan, MSc.Ph.D.Student, Division of Pharmacology, Otto Loewi Research Center Medical University of Graz

Chronic inflammatory lung diseases such as asthma have a strong circadian signature. In this paper Srinivasn and colleagues highlight the time-of-day response in lung inflammation observing altered clock genes expression due to chronic HDM exposure. Further, allergen exposure during active phase compared to resting phase, resulted in an exaggerated inflammatory response including an increased infiltration of immune cells, enhanced eosinophil associated chemokines, Th2 gene expression, cytokine release and immunoglobulin concentrations. This excessive immune response exhibited gender differences such as increased infiltration of eosinophil subsets, enhanced eotaxin levels and increased IL13 gene expression, only observed in females. In summary, both daytime and sex-based differences were observed in immune infiltration, humoral response, and chemokine and cytokine responses to chronic HDM-induced pulmonary inflammation.

Last updated: February 27, 2024

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