RXRα Regulates the Development of Resident Tissue Macrophages

Overview

Journal Immunohorizons

Specialty Allergy & Immunology

Date 2022 Jun 22

PMID 35732333

Authors

Jordan Philpott

Simon Kazimierczyk

Parimal Korgaonkar

Evan Bordt

Jaclyn Zois

Chithirachelvi Vasudevan

Di Meng

Ishan Bhatia

Naifang Lu

Brittany Jimena

Caryn Porter

Bobby J Cherayil

Nitya Jain

Affiliations

Soon will be listed here.

Abstract

Resident tissue macrophages (RTMs) develop from distinct waves of embryonic progenitor cells that seed tissues before birth. Tissue-specific signals drive a differentiation program that leads to the functional specialization of RTM subsets. Genetic programs that regulate the development of RTMs are incompletely understood, as are the mechanisms that enable their maintenance in adulthood. In this study, we show that the ligand-activated nuclear hormone receptor, retinoid X receptor (RXR)α, is a key regulator of murine RTM development. Deletion of RXRα in hematopoietic precursors severely curtailed RTM populations in adult tissues, including the spleen, peritoneal cavity, lung, and liver. The deficiency could be traced to the embryonic period, and mice lacking RXRα in hematopoietic lineages had greatly reduced numbers of yolk sac and fetal liver macrophages, a paucity that persisted into the immediate postnatal period.

Citing Articles

A pan-family screen of nuclear receptors in immunocytes reveals ligand-dependent inflammasome control.

Wang Y, Zhang Y, Kim K, Han J, Okin D, Jiang Z Immunity. 2024; 57(12):2737-2754.e12.

PMID: 39571575 PMC: 11634661. DOI: 10.1016/j.immuni.2024.10.010.

GDF2 and BMP10 coordinate liver cellular crosstalk to maintain liver health.

Zhao D, Huang Z, Li X, Wang H, Hou Q, Wang Y Elife. 2024; 13.

PMID: 39453386 PMC: 11509670. DOI: 10.7554/eLife.95811.

Resolving Resident Colonic Muscularis Macrophage Diversity and Plasticity During Colitis.

Ohishi K, Dora D, Han C, Guyer R, Ohkura T, Kazimierczyk S Inflamm Bowel Dis. 2024; 31(1):151-168.

PMID: 39102823 PMC: 11701110. DOI: 10.1093/ibd/izae155.

Gonadal hormones impart male-biased behavioral vulnerabilities to immune activation via microglial mitochondrial function.

Bordt E, Moya H, Jo Y, Ravichandran C, Bankowski I, Ceasrine A Brain Behav Immun. 2023; 115:680-695.

PMID: 37972878 PMC: 10996880. DOI: 10.1016/j.bbi.2023.11.010.

Retinoid X Receptor agonists as selective modulators of the immune system for the treatment of cancer.

Leal A, Hung P, Chowdhury A, Liby K Pharmacol Ther. 2023; 252:108561.

PMID: 37952906 PMC: 10704405. DOI: 10.1016/j.pharmthera.2023.108561.

References

Schneider C, Nobs S, Kurrer M, Rehrauer H, Thiele C, Kopf M . Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat Immunol. 2014; 15(11):1026-37. DOI: 10.1038/ni.3005. View

Ennamorati M, Vasudevan C, Clerkin K, Halvorsen S, Verma S, Ibrahim S . Intestinal microbes influence development of thymic lymphocytes in early life. Proc Natl Acad Sci U S A. 2020; 117(5):2570-2578. PMC: 7007548. DOI: 10.1073/pnas.1915047117. View

Shimshek D, Kim J, Hubner M, Spergel D, Buchholz F, Casanova E . Codon-improved Cre recombinase (iCre) expression in the mouse. Genesis. 2002; 32(1):19-26. DOI: 10.1002/gene.10023. View

Bleriot C, Chakarov S, Ginhoux F . Determinants of Resident Tissue Macrophage Identity and Function. Immunity. 2020; 52(6):957-970. DOI: 10.1016/j.immuni.2020.05.014. View

Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K . A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science. 2012; 336(6077):86-90. DOI: 10.1126/science.1219179. View

Nunez V, Alameda D, Rico D, Mota R, Gonzalo P, Cedenilla M . Retinoid X receptor alpha controls innate inflammatory responses through the up-regulation of chemokine expression. Proc Natl Acad Sci U S A. 2010; 107(23):10626-31. PMC: 2890831. DOI: 10.1073/pnas.0913545107. View

Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S . Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010; 330(6005):841-5. PMC: 3719181. DOI: 10.1126/science.1194637. View

Dawson M, Xia Z . The retinoid X receptors and their ligands. Biochim Biophys Acta. 2011; 1821(1):21-56. PMC: 4097889. DOI: 10.1016/j.bbalip.2011.09.014. View

Lavin Y, Mortha A, Rahman A, Merad M . Regulation of macrophage development and function in peripheral tissues. Nat Rev Immunol. 2015; 15(12):731-44. PMC: 4706379. DOI: 10.1038/nri3920. View

10.

Casanova-Acebes M, Menendez-Gutierrez M, Porcuna J, Alvarez-Errico D, Lavin Y, Garcia A . RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression. Nat Commun. 2020; 11(1):1655. PMC: 7125161. DOI: 10.1038/s41467-020-15371-0. View

11.

Guilliams M, de Kleer I, Henri S, Post S, Vanhoutte L, De Prijck S . Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J Exp Med. 2013; 210(10):1977-92. PMC: 3782041. DOI: 10.1084/jem.20131199. View

12.

Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L . Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature. 2014; 518(7540):547-51. PMC: 5997177. DOI: 10.1038/nature13989. View

13.

Roszer T, Menendez-Gutierrez M, Cedenilla M, Ricote M . Retinoid X receptors in macrophage biology. Trends Endocrinol Metab. 2013; 24(9):460-8. DOI: 10.1016/j.tem.2013.04.004. View

14.

Liu Z, Gu Y, Shin A, Zhang S, Ginhoux F . Analysis of Myeloid Cells in Mouse Tissues with Flow Cytometry. STAR Protoc. 2020; 1(1):100029. PMC: 7580097. DOI: 10.1016/j.xpro.2020.100029. View

15.

Hoeffel G, Chen J, Lavin Y, Low D, Almeida F, See P . C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity. 2015; 42(4):665-78. PMC: 4545768. DOI: 10.1016/j.immuni.2015.03.011. View

16.

Ogilvy S, Metcalf D, Gibson L, Bath M, Harris A, Adams J . Promoter elements of vav drive transgene expression in vivo throughout the hematopoietic compartment. Blood. 1999; 94(6):1855-63. View

17.

Sheng J, Ruedl C, Karjalainen K . Most Tissue-Resident Macrophages Except Microglia Are Derived from Fetal Hematopoietic Stem Cells. Immunity. 2015; 43(2):382-93. DOI: 10.1016/j.immuni.2015.07.016. View

18.

Gautier E, Chow A, Spanbroek R, Marcelin G, Greter M, Jakubzick C . Systemic analysis of PPARγ in mouse macrophage populations reveals marked diversity in expression with critical roles in resolution of inflammation and airway immunity. J Immunol. 2012; 189(5):2614-24. PMC: 3537497. DOI: 10.4049/jimmunol.1200495. View

19.

Mass E, Ballesteros I, Farlik M, Halbritter F, Gunther P, Crozet L . Specification of tissue-resident macrophages during organogenesis. Science. 2016; 353(6304). PMC: 5066309. DOI: 10.1126/science.aaf4238. View

20.

Ma F, Liu S, Razani B, Arora N, Li B, Kagechika H . Retinoid X receptor α attenuates host antiviral response by suppressing type I interferon. Nat Commun. 2014; 5:5494. PMC: 4380327. DOI: 10.1038/ncomms6494. View