Clr-f expression regulates kidney immune and metabolic homeostasis

• Published in: Scientific reports Vol. 12; no. 1; p. 4834
• Main Authors: Zein, Haggag S., Abou-Samra, Elias, Scur, Michal, Gutsol, Alex, Hall, Clayton W., Dasgupta, Bishal, Gharibeh, Lara, Abujamel, Turki, Medina-Luna, Daniel, Gamage, Gayani S., Pelino, Tessa J., Nemer, Mona, Rahim, Mir Munir A., Steinle, Alexander, Parsons, Brendon D., Makrigiannis, Andrew P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4022/1585/104; 692/420/2780/262; Animals; Complement component C3; Homeostasis; Humanities and Social Sciences; Immune response; Inflammation; Interleukin 12; Kidney - metabolism; Kidneys; Killer Cells, Natural; Lectins; Lectins, C-Type - metabolism; Leukocytes (neutrophilic); Lipids; Lymphocytes; Lymphocytes B; Metabolism; Mice; Mice, Inbred C57BL; multidisciplinary; NK Cell Lectin-Like Receptor Subfamily B - metabolism; RAG1 protein; Science; Science (multidisciplinary); Transcription; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-08547-9

The C-type lectin-related protein, Clr-f, encoded by Clec2h in the mouse NK gene complex (NKC), is a member of a family of immune regulatory lectins that guide immune responses at distinct tissues of the body. Clr-f is highly expressed in the kidney; however, its activity in this organ is unknown. To assess the requirement for Clr-f in kidney health and function, we generated a Clr-f-deficient mouse ( Clr-f −/− ) by targeted deletions in the Clec2h gene. Mice lacking Clr-f exhibited glomerular and tubular lesions, immunoglobulin and C3 complement protein renal deposits, and significant abdominal and ectopic lipid accumulation. Whole kidney transcriptional profile analysis of Clr-f −/− mice at 7, 13, and 24 weeks of age revealed a dynamic dysregulation in lipid metabolic processes, stress responses, and inflammatory mediators. Examination of the immune contribution to the pathologies of Clr-f −/− mouse kidneys identified elevated IL-12 and IFNγ in cells of the tubulointerstitium, and an infiltrating population of neutrophils and T and B lymphocytes. The presence of these insults in a Rag1 −/− Clr-f −/− background reveals that Clr-f −/− mice are susceptible to a T and B lymphocyte-independent renal pathogenesis. Our data reveal a role for Clr-f in the maintenance of kidney immune and metabolic homeostasis.