Macrophage Dysfunction Initiates Colitis During Weaning of Infant Mice Lacking the Interleukin-10 Receptor

Overview

Journal Elife

Specialty Biology

Date 2017 Jul 6

PMID 28678006

Citations 22

Authors

Naresh S Redhu

Vasudevan Bakthavatchalu

Evan A Conaway

Dror S Shouval

Amy Tsou

Jeremy A Goettel

Amlan Biswas

Chuanwu Wang

Michael Field

Werner Muller

Andre Bleich

Ning Li

Georg K Gerber

Lynn Bry

James G Fox

Scott B Snapper

Bruce H Horwitz

Affiliations

Soon will be listed here.

Abstract

Infants with defects in the interleukin 10 receptor (IL10R) develop very early onset inflammatory bowel disease. Whether IL10R regulates lamina propria macrophage function during infant development in mice and whether macrophage-intrinsic IL10R signaling is required to prevent colitis in infancy is unknown. Here we show that although signs of colitis are absent in IL10R-deficient mice during the first two weeks of life, intestinal inflammation and macrophage dysfunction begin during the third week of life, concomitant with weaning and accompanying diversification of the intestinal microbiota. However, IL10R did not directly regulate the microbial ecology during infant development. Interestingly, macrophage depletion with clodronate inhibited the development of colitis, while the absence of IL10R specifically on macrophages sensitized infant mice to the development of colitis. These results indicate that IL10R-mediated regulation of macrophage function during the early postnatal period is indispensable for preventing the development of murine colitis.

Citing Articles

Huang Lian Jie Du decoction attenuated colitis via suppressing the macrophage Csf1r/Src pathway and modulating gut microbiota.

Su S, Liu T, Zheng J, Wu H, Keng V, Zhang S Front Immunol. 2024; 15:1375781.

PMID: 39391314 PMC: 11464287. DOI: 10.3389/fimmu.2024.1375781.

Oral administration of Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 ameliorates DSS-induced colitis in mice.

Zhang M, Xu X, Su L, Zeng Y, Lin J, Li W J Nanobiotechnology. 2024; 22(1):607.

PMID: 39379937 PMC: 11463058. DOI: 10.1186/s12951-024-02856-z.

Cytokine Profile in Predicting the Effectiveness of Advanced Therapy for Ulcerative Colitis: A Narrative Review.

Kurumi H, Yokoyama Y, Hirano T, Akita K, Hayashi Y, Kazama T Biomedicines. 2024; 12(5).

PMID: 38790914 PMC: 11117845. DOI: 10.3390/biomedicines12050952.

Akkermansia muciniphila-induced trained immune phenotype increases bacterial intracellular survival and attenuates inflammation.

Pena-Cearra A, Palacios A, Pellon A, Castelo J, Tanner Pasco S, Seoane I Commun Biol. 2024; 7(1):192.

PMID: 38365881 PMC: 10873422. DOI: 10.1038/s42003-024-05867-6.

OGR1 (GPR68) and TDAG8 (GPR65) Have Antagonistic Effects in Models of Colonic Inflammation.

Perren L, Busch M, Schuler C, Ruiz P, Foti F, Weibel N Int J Mol Sci. 2023; 24(19).

PMID: 37834303 PMC: 10573511. DOI: 10.3390/ijms241914855.

References

Kang S, Bloom S, Norian L, Geske M, Flavell R, Stappenbeck T . An antibiotic-responsive mouse model of fulminant ulcerative colitis. PLoS Med. 2008; 5(3):e41. PMC: 2270287. DOI: 10.1371/journal.pmed.0050041. View

Becker C, Fantini M, Neurath M . High resolution colonoscopy in live mice. Nat Protoc. 2007; 1(6):2900-4. DOI: 10.1038/nprot.2006.446. View

Shannon C . The mathematical theory of communication. 1963. MD Comput. 1997; 14(4):306-17. View

DeSantis T, Hugenholtz P, Larsen N, Rojas M, Brodie E, Keller K . Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol. 2006; 72(7):5069-72. PMC: 1489311. DOI: 10.1128/AEM.03006-05. View

Blacher E, Levy M, Tatirovsky E, Elinav E . Microbiome-Modulated Metabolites at the Interface of Host Immunity. J Immunol. 2017; 198(2):572-580. DOI: 10.4049/jimmunol.1601247. View

Hoshi N, Schenten D, Nish S, Walther Z, Gagliani N, Flavell R . MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice. Nat Commun. 2012; 3:1120. PMC: 3521499. DOI: 10.1038/ncomms2113. View

Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy A, Friedlander G . Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity. 2012; 37(6):1076-90. DOI: 10.1016/j.immuni.2012.08.026. View

Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W . Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993; 75(2):263-74. DOI: 10.1016/0092-8674(93)80068-p. View

Muthupalani S, Ge Z, Feng Y, Rickman B, Mobley M, McCabe A . Systemic macrophage depletion inhibits Helicobacter bilis-induced proinflammatory cytokine-mediated typhlocolitis and impairs bacterial colonization dynamics in a BALB/c Rag2-/- mouse model of inflammatory bowel disease. Infect Immun. 2012; 80(12):4388-97. PMC: 3497414. DOI: 10.1128/IAI.00530-12. View

10.

Garrett W, Lord G, Punit S, Lugo-Villarino G, Mazmanian S, Ito S . Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. 2007; 131(1):33-45. PMC: 2169385. DOI: 10.1016/j.cell.2007.08.017. View

11.

Donnelly R, Sheikh F, Kotenko S, Dickensheets H . The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol. 2004; 76(2):314-21. DOI: 10.1189/jlb.0204117. View

12.

Spencer S, Di Marco F, Hooley J, Bauer M, Ryan A, Sordat B . The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor. J Exp Med. 1998; 187(4):571-8. PMC: 2212143. DOI: 10.1084/jem.187.4.571. View

13.

Bain C, Bravo-Blas A, Scott C, Gomez Perdiguero E, Geissmann F, Henri S . Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol. 2014; 15(10):929-937. PMC: 4169290. DOI: 10.1038/ni.2967. View

14.

Saraiva M, OGarra A . The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010; 10(3):170-81. DOI: 10.1038/nri2711. View

15.

Uhlig H, Schwerd T, Koletzko S, Shah N, Kammermeier J, Elkadri A . The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology. 2014; 147(5):990-1007.e3. PMC: 5376484. DOI: 10.1053/j.gastro.2014.07.023. View

16.

Moran C, Walters T, Guo C, Kugathasan S, Klein C, Turner D . IL-10R polymorphisms are associated with very-early-onset ulcerative colitis. Inflamm Bowel Dis. 2012; 19(1):115-23. PMC: 3744177. DOI: 10.1002/ibd.22974. View

17.

Glocker E, Kotlarz D, Klein C, Shah N, Grimbacher B . IL-10 and IL-10 receptor defects in humans. Ann N Y Acad Sci. 2012; 1246:102-7. DOI: 10.1111/j.1749-6632.2011.06339.x. View

18.

Moore K, de Waal Malefyt R, Coffman R, OGarra A . Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001; 19:683-765. DOI: 10.1146/annurev.immunol.19.1.683. View

19.

Powell N, Walker A, Stolarczyk E, Canavan J, Gokmen M, Marks E . The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells. Immunity. 2012; 37(4):674-84. PMC: 3540260. DOI: 10.1016/j.immuni.2012.09.008. View

20.

Kotlarz D, Beier R, Murugan D, Diestelhorst J, Jensen O, Boztug K . Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy. Gastroenterology. 2012; 143(2):347-55. DOI: 10.1053/j.gastro.2012.04.045. View