Lamina propria lymphocytes in sanroque mice produce proinflammatory cytokines that drive chronic small intestinal inflammation

• Published in: The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.65-65.11
• Main Authors: Klein, John R, Williams, Alexander, Vigneswaran, Nadarajah, Montufar-Solis, Dina
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.65.11

Roquin is an E3 ligase that regulates mRNA stability. Mice with a mutation in the Rc3h1 gene and Roquin protein, referred to as Roquinsan/san or sanroque mice, develop extensive chronic inflammation and autoimmune pathologies. Our laboratory recently reported that beginning at 8 weeks of age sanroque mice also develop inflammation that is localized to the small intestine but is rare in the colon. Here, we demonstrate that small intestinal intraepithelial lymphocytes (IELs) are present in the epithelium of sanroque mice, but that cell recoverability is low using standard extraction techniques even though lamina propria lymphocytes (LPLs) can be recovered in normal numbers. In characterizing T cell costimulatory markers and activation molecules on LPLs in sanroque mice, we identified Ly6C and 4-1BB (CD137) as being expressed at elevated levels on small intestinal LPLs, and we show that both subsets, in conjunction with cells expressing the KLRG1 T cell activation molecule, are sources of the IL-17A, IFN-γ, and TNFα proinflammatory cytokines. TNFα was primarily produced by 4-1BB+, KLRG1− cells, but was also made by some 4-1BB−, KLRG1− cells, and 4-1BB−, KLRG1+ cells. These findings collectively suggest that the small intestinal inflammatory response in sanroque mice is driven, at least in part, by LPL activation through Ly6C, 4-1BB, and KLRG1 signaling, and they provide further evidence demonstrating the utility of using the sanroque mouse as an animal model of chronic inflammation in the small intestine.