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Immune Complex Clearance by Kuppfer Cells: Why a Healthy Liver is Crucial in Preventing Autoimmune Diseases

Written by Portland Clinic of Natural Health on August 22, 2023

The human body's immune system has a fascinating and intricate defense mechanism that involves myriad cells, tissues, and proteins. Among these are immune complexes, which are formed when antibodies in the bloodstream bind to antigens (foreign substances).

In a healthy state, immune complexes are beneficial as they help neutralize and remove threats from the body. However, when these complexes accumulate and aren't efficiently cleared, they can deposit in various tissues, leading to inflammation and conditions like autoimmune diseases.

Here's where the liver, particularly Kupffer cells, plays a pivotal role.

Role of Kupffer Cells in Immune Complex Clearance

Kupffer cells are specialized macrophages (a type of white blood cell) located in the liver. One of their primary functions is to engulf and break down aged red blood cells, bacteria, and other debris. In addition to this, they are adept at clearing immune complexes from the bloodstream. (1, 2)

Evidence from scientific studies has shown that Kupffer cells have receptors called Fc receptors that can recognize and bind to immune complexes. Once bound, these complexes are internalized and degraded, thus preventing their accumulation in the bloodstream. (3, 4)

Impaired Liver Function and Its Implications

The liver plays multiple roles, including detoxification of harmful substances, metabolism of drugs, and clearing pathogens and immune complexes. When the liver is compromised, whether due to inflammation, fatty liver disease, or systemic toxicity, its ability to perform these tasks efficiently is hampered.

A compromised liver means Kupffer cells might not function optimally. This inefficiency can result in:

  • Accumulation of immune complexes in the bloodstream.
  • Deposition of these complexes in various tissues, leading to inflammation.
  • Potential triggering or exacerbation of autoimmune diseases.

The Link Between Liver Health and Autoimmune Diseases

Several studies have highlighted the correlation between liver health and the prevalence of autoimmune diseases. For instance, patients with autoimmune diseases often have liver abnormalities. Conversely, conditions like non-alcoholic fatty liver disease (NAFLD) are associated with a higher risk of developing autoimmune disorders. (5, 6)

This bidirectional relationship is not fully understood, but impaired clearance of immune complexes by an unhealthy liver is believed to be a significant contributor.

The liver, with its army of Kupffer cells, is a crucial player in maintaining the delicate balance of the immune system. It's vital to ensure the liver remains in optimal condition, not only for detoxification and metabolism but also to prevent the onset or exacerbation of autoimmune conditions. Lifestyle choices, including a balanced diet, moderate alcohol consumption, and regular exercise, can contribute to liver health and, by extension, a robust immune system.


  1. Johansson AG, Sundqvist T, Skogh T. IgG immune complex binding to and activation of liver cells. An in vitro study with IgG immune complexes, Kupffer cells, sinusoidal endothelial cells and hepatocytes. Int Arch Allergy Immunol. 2000 Apr;121(4):329-36. doi: 10.1159/000024347. PMID: 10828724.
  2. Yan J, Vetvicka V, Xia Y, Hanikýrová M, Mayadas TN, Ross GD. Critical role of Kupffer cell CR3 (CD11b/CD18) in the clearance of IgM-opsonized erythrocytes or soluble beta-glucan. Immunopharmacology. 2000 Jan;46(1):39-54. doi: 10.1016/s0162-3109(99)00157-5. PMID: 10665778.
  3. Nishi T, Bhan AK, Collins AB, McCluskey RT. Effect of circulating immune complexes on Fc and C3 receptors of Kupffer cells in vivo. Lab Invest. 1981 May;44(5):442-8. PMID: 7230730.
  4. Mannik M. Physicochemical and functional relationships of immune complexes. J Invest Dermatol. 1980 May;74(5):333-8. doi: 10.1111/1523-1747.ep12543582. PMID: 6446581.
  5. Zeng Q, Zhao L, Wang C, Gao M, Han X, Chen C, Tu C, Han P, Li J. Relationship between autoimmune liver disease and autoimmune thyroid disease: a cross-sectional study. Scand J Gastroenterol. 2020 Feb;55(2):216-221. doi: 10.1080/00365521.2019.1710766. Epub 2020 Feb 21. PMID: 32083943.
  6. Strzepka J, Schwartz BA, Ritz EM, Aloman C, Reau N. Patients With Autoimmune Hepatitis and Nonalcoholic Fatty Liver Disease: Characteristics, Treatment, and Outcomes. J Clin Gastroenterol. 2022 Dec 20. doi: 10.1097/MCG.0000000000001817. Epub ahead of print. PMID: 36729430.

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