The Gut Epithelial Receptor LRRC19 Promotes the Recruitment of Immune Cells and Gut Inflammation.

Commensal microbes are necessary for a healthy gut immune system. However, the mechanism involving these microbes that establish and maintain gut immune responses is largely unknown. Here, we have found that the gut immune receptor leucine-rich repeat (LRR) C19 is involved in host-microbiota interactions. LRRC19 deficiency not only impairs the gut immune system but also reduces inflammatory responses in gut tissues. We demonstrate that the LRRC19-associated chemokines CCL6, CCL9, CXCL9, and CXCL10 play a critical role in immune cell recruitment and intestinal inflammation. The expression of these chemokines is associated with regenerating islet-derived (REG) protein-mediated microbiotas. We also found that the expression of REGs may be regulated by gut Lactobacillus through LRRC19-mediated activation of NF-κB. Therefore, our study establishes a regulatory axis of LRRC19, REGs, altered microbiotas, and chemokines for the recruitment of immune cells and the regulation of intestinal inflammation.

LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent infection by uropathogenic bacteria.

The innate immune-dependent bactericidal effects are critical for preventing microbial colonization in the urinary system. However, the mechanisms involved in establishing innate immune responses in kidney are not completely understood. Here we describe the role of a novel member of the LRR (leucine-rich repeat) class of transmembrane proteins, LRRC19 (LRR-containing 19) in eliminating uropathogenic bacteria. LRRC19 is predominantly expressed in human and mouse kidney tubular epithelial cells and LRRC19-deficient mice are more susceptible to uropathogenic Escherichia coli (UPEC) infection than wild-type or TLR4 knockout mice. Recognition of UPEC by LRRC19 induces the production of cytokines, chemokines and antimicrobial substances through TRAF2- and TRAF6-mediated NF-κB and MAPK signalling pathways. Thus, LRRC19 may be a critical pathogen-recognition receptor in kidney mediating the elimination of UPEC infection.

Multiple tumor-associated microRNAs modulate the survival and longevity of dendritic cells by targeting YWHAZ and Bcl2 signaling pathways.

Tumors use a wide array of immunosuppressive strategies, such as reducing the longevity and survival of dendritic cells (DCs), to diminish immune responses and limit the effect of immunotherapy. In this study, we found that tumors upregulate the expression of multiple microRNAs (miRNAs), such as miR-16-1, miR-22, miR-155, and miR-503. These tumor-associated miRNAs influenced the survival and longevity of DCs by affecting the expression of multiple molecules that are associated with apoptotic signaling pathways. Specifically, miR-22 targeted YWHAZ to interrupt the PI3K/Akt and MAPK signaling pathways, and miR-503 downregulated Bcl2 expression. The result of the increased expression of miR-22 and miR-503 in the tumor-associated DCs was their reduced survival and longevity. Thus, tumor-associated miRNAs can target multiple intracellular signaling molecules to cause the apoptosis of DCs in the tumor environment. Use of miR-22 and miR-503 as inhibitors may therefore represent a new strategy to improve DC-based immunotherapies against tumors.