Differential Roles for Interleukin-23 and Interleukin-17 in Intestinal Immunoregulation.

Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE

Publication: Cambridge, MA : Cell Press
Original Publication: Cambridge, Mass. : Cell Press, c1994-

Colitis/*immunology ; Interleukin-17/*physiology ; Interleukin-23/*physiology ; Receptors, Interleukin-17/*physiology; ATP Binding Cassette Transporter, Subfamily B/deficiency ; Animals ; Colitis/drug therapy ; Colitis/etiology ; Colitis/microbiology ; Disease Models, Animal ; Disease Progression ; Epithelium/physiopathology ; Female ; Forkhead Transcription Factors/analysis ; Gene Expression Regulation/immunology ; Helicobacter Infections/complications ; Helicobacter Infections/immunology ; Immunization, Passive ; Immunoglobulin G/therapeutic use ; Interleukin-12 Subunit p40/antagonists & inhibitors ; Interleukin-17/immunology ; Interleukin-23/immunology ; Interleukin-23 Subunit p19/antagonists & inhibitors ; Interleukin-23 Subunit p19/immunology ; Intestinal Mucosa/physiopathology ; Mice ; Mice, Knockout ; Permeability ; Receptors, Interleukin-17/antagonists & inhibitors ; Receptors, Interleukin-17/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Transcriptome

Interleukin-23 (IL-23) and IL-17 are cytokines currently being targeted in clinical trials. Although inhibition of both of these cytokines is effective for treating psoriasis, IL-12 and IL-23 p40 inhibition attenuates Crohn's disease, whereas IL-17A or IL-17 receptor A (IL-17RA) inhibition exacerbates Crohn's disease. This dichotomy between IL-23 and IL-17 was effectively modeled in the multidrug resistance-1a-ablated (Abcb1a(-/-)) mouse model of colitis. IL-23 inhibition attenuated disease by decreasing colonic inflammation while enhancing regulatory T (Treg) cell accumulation. Exacerbation of colitis by IL-17A or IL-17RA inhibition was associated with severe weakening of the intestinal epithelial barrier, culminating in increased colonic inflammation and accelerated mortality. These data show that IL-17A acts on intestinal epithelium to promote barrier function and provide insight into mechanisms underlying exacerbation of Crohn's disease when IL-17A or IL-17RA is inhibited.
(Copyright © 2015 Elsevier Inc. All rights reserved.)

Comment in: Immunity. 2015 Oct 20;43(4):620-2. (PMID: 26488809)

GEO GSE72212

0 (ATP Binding Cassette Transporter, Subfamily B)
0 (Forkhead Transcription Factors)
0 (Foxp3 protein, mouse)
0 (Il17ra protein, mouse)
0 (Immunoglobulin G)
0 (Interleukin-12 Subunit p40)
0 (Interleukin-17)
0 (Interleukin-23)
0 (Interleukin-23 Subunit p19)
0 (Receptors, Interleukin-17)
9EI49ZU76O (multidrug resistance protein 3)

Date Created: 20151004 Date Completed: 20160201 Latest Revision: 20220410

20231215

10.1016/j.immuni.2015.08.019

26431947