Clr-f expression regulates kidney immune and metabolic homeostasis

Haggag S Zein; Elias Abou-Samra; Michal Scur; Alex Gutsol; Clayton W Hall; Bishal Dasgupta; Lara Gharibeh; Turki Abujamel; Daniel Medina-Luna; Gayani S Gamage; Tessa J Pelino; Mona Nemer; Mir Munir A Rahim; Alexander Steinle; Brendon D Parsons; Andrew P Makrigiannis

doi:10.1038/s41598-022-08547-9

Clr-f expression regulates kidney immune and metabolic homeostasis

Sci Rep. 2022 Mar 22;12(1):4834. doi: 10.1038/s41598-022-08547-9.

Authors

Haggag S Zein^#^{1

2}, Elias Abou-Samra^#³, Michal Scur¹, Alex Gutsol⁴, Clayton W Hall⁵, Bishal Dasgupta¹, Lara Gharibeh^{6

7}, Turki Abujamel^{8

9}, Daniel Medina-Luna^{1

10}, Gayani S Gamage¹, Tessa J Pelino¹, Mona Nemer³, Mir Munir A Rahim¹¹, Alexander Steinle^{12

13}, Brendon D Parsons^{14

15}, Andrew P Makrigiannis^{16

17

18}

Affiliations

¹ Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
² King Abdullah International Medical Research Centre, Immunology Research Program, Riyadh, Saudi Arabia.
³ Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
⁴ Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
⁵ Department of Pathology and Molecular Medicine, Division of Medical Microbiology, McMaster University, Hamilton, ON, Canada.
⁶ Molecular Genetics and Cardiac Regeneration Laboratory, Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
⁷ Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, ON, Canada.
⁸ Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
⁹ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
¹⁰ Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada.
¹¹ Department of Biomedical Sciences, University of Windsor, Windsor, ON, Canada.
¹² Institute for Molecular Medicine, Goethe University Frankfurt, Frankfurt am Main, Germany.
¹³ Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt am Main, Germany.
¹⁴ Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada. brendonp@dal.ca.
¹⁵ Department of Microbiology and Immunology, Dalhousie University, Sir Charles Tupper Medical Building, Rm. 7-F2, 5850 College Street, Halifax, NS, B3H 4R2, Canada. brendonp@dal.ca.
¹⁶ Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada. andrew.makrigiannis@dal.ca.
¹⁷ Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada. andrew.makrigiannis@dal.ca.
¹⁸ Department of Microbiology and Immunology, Dalhousie University, Sir Charles Tupper Medical Building, Rm. 7-B2, 5850 College Street, Halifax, NS, B3H 4R2, Canada. andrew.makrigiannis@dal.ca.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Homeostasis
Kidney / metabolism
Killer Cells, Natural*
Lectins, C-Type* / metabolism
Lipids
Mice
Mice, Inbred C57BL
NK Cell Lectin-Like Receptor Subfamily B / metabolism

Substances

Lectins, C-Type
Lipids
NK Cell Lectin-Like Receptor Subfamily B