Primary cilia and their effects on immune cell functions and metabolism: a model

A Western lifestyle triggers a subclinical immune response, also called metaflammation in humans and mice. Metaflammation is now thought to underlie the development of certain noncommunicable diseases associated with obesity. One of the major symptoms of the Bardet–Biedl Syndrome (BBS) ciliopathy in humans and mice is obesity; however, depending on the BBS mutation and age, the severity of metabolic syndrome varies. Primary cilia evoke cell-autonomous (in cytotoxic CD8+ T cells) and noncell-autonomous responses (in B lymphocytes and macrophages) that can control certain immune cell functions in humans and mice. Primary cilia dysfunction leading to ciliopathies can evoke tissue-specific responses in immune cells in humans and mice. Primary cilia are hair-like protrusions of the plasma membrane that function as cellular antennae and are present on most cells in the human body. Primary cilia dysfunction leads to severe diseases, commonly termed ‘ciliopathies’. A significant symptom of certain ciliopathies is obesity, and current research aims to identify contributing mechanisms of obesity development in these patients. Western lifestyle-associated factors can trigger chronic inflammation, or metaflammation, which can also attribute to obesity-associated metabolic disorders. However, obese individuals can also be ‘metabolically healthy’, as discussed for a subset of patients with obesity and ciliopathy. Here, we propose that primary cilia signaling might modulate specific immune cell phenotypes, behaviors, and functions, which might impact inflammatory responses in the context of ciliopathies and beyond. Primary cilia are hair-like protrusions of the plasma membrane that function as cellular antennae and are present on most cells in the human body. Primary cilia dysfunction leads to severe diseases, commonly termed ‘ciliopathies’. A significant symptom of certain ciliopathies is obesity, and current research aims to identify contributing mechanisms of obesity development in these patients. Western lifestyle-associated factors can trigger chronic inflammation, or metaflammation, which can also attribute to obesity-associated metabolic disorders. However, obese individuals can also be ‘metabolically healthy’, as discussed for a subset of patients with obesity and ciliopathy. Here, we propose that primary cilia signaling might modulate specific immune cell phenotypes, behaviors, and functions, which might impact inflammatory responses in the context of ciliopathies and beyond. signaling proteins secreted by adipocytes. chronic skin inflammation. mutation in one allele of PKD1 or PKD2 causes cyst development in the kidney. develops due to mutations in one of 26 different BBS genes that cause primary cilia dysfunction. protein complex at the base of the primary cilium, comprising eight BBS proteins that control protein localization in the primary cilium. signaling in primary cilia. diseases that develop due to primary cilia dysfunction. transmembrane proteins that sense external stimuli and transduce this information via G proteins and second messenger signaling into a cellular response. formed between an antigen-presenting cell and a lymphocyte; here, we refer to the IS in cytotoxic CD8+ T cells. transport machinery that moves proteins in and out of the cilium along microtubule tracks. a low-grade, chronic inflammation that can result in metabolic dysfunction. normal blood pressure. hair-like, solitary membrane protrusions found on most vertebrate cells; function as cellular antennae. mutation in both alleles of an NPHP gene causes cyst development in the kidney. CD4+ T cell subset known to suppress the immune response. increase in the bile duct size and dilated bile duct lumen.