Cell Metabolism Chill stimulates the immune system and relieves inflammation of the nervous system

Written | Hu Xiaohua's immune response usually requires a lot of energy [1]
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In addition, there are many other physiological reactions that consume a lot of energy, such as the body's adaptation to the cold environment
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So, is there a competitive relationship between these two high-energy-consuming physiological processes? This is not only a very interesting scientific question, but also has important pathological significance for some immune diseases (such as autoimmune diseases)
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Multiple sclerosis (MS) is the most common autoimmune demyelinating disease of the central nervous system (CNS)
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Currently, experimental autoimmune encephalomyelitis (EAE) is the most commonly used animal model of multiple sclerosis (MS)
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Previous studies have shown that CD4+ T cells and monocytes play an important role in the pathogenesis of EAE.
Among them, monocytes and monocyte-derived cells can perform antigen presentation functions by up-regulating the expression of MHCII, and ultimately initiate self-response Sex T cells destroy the tissues of the CNS [2]
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Then, whether cold exposure will inhibit the activation of monocyte-mediated autoreactive T cells, thereby helping to alleviate the autoimmunity of the CNS, is currently unclear
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On October 22, 2021, a team from Mirko Trajkovski, Department of Cell Physiology and Metabolism, University of Geneva, Switzerland, and Doron Merkler, Department of Pathology and Immunology, published a research article on Cell Metabolism entitled Cold exposure protects from neuroinflammation through immunologic reprogramming, revealing Cold stimulation will reshape the immune state of monocytes in the bone marrow, thereby alleviating the inflammatory response of the nervous system
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First, in order to explore the effect of cold exposure on the immune system, the author performed RNA-seq analysis on the bone marrow of mice fed at room temperature and cold environment (10°C) for 2 weeks, and enriched a lot of it is very important for the activation and differentiation of myeloid cells.
Important genes
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Through further flow cytometry analysis, the authors noticed that cold exposure specifically reduces the number of Ly6Chi monocytes and their MHCII expression, but does not change the number and activity of other immune cells
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Considering that β3-adrenergic receptor (β3-AR) signaling is one of the main ways to be activated in a cold environment [3], the authors found that β3-AR agonists are sufficient to simulate the physiological effects of cold exposure
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Therefore, these experimental results together show that cold exposure will reshape the immune state of Ly6Chi monocytes, and this process depends on the activation of β3-adrenergic receptor signals
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Next, the author explored the physiological functions of this process in different inflammation models
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The author first promoted the inflammatory phenotype by subcutaneous injection of B16-GM-CSF tumor cells to increase the number of monocytes in the circulatory system and the expression of MHCII
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On this basis, the authors found that cold exposure reduces the expression of MHCII in mouse Ly6Chi monocytes, but does not affect other immune cell populations
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In addition, the authors also observed a similar phenomenon in the peritoneal inflammation model caused by thioglycolic acid
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Therefore, different inflammation models have shown that cold exposure will reduce the expression of MHCII in monocytes, but will not affect lymphatic drainage
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Considering that Ly6Chi monocytes are the key effector cells of CNS autoimmune diseases (such as MS), the authors proceeded to explore in EAE model mice
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The authors found that cold exposure significantly improved the phenotype of mouse EAE (test indicators include disease score, time to first onset, etc.
), and the authors found that 2 days of cold exposure was sufficient to bring about significant improvements
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In contrast, heat exposure (34°C, 7 days) can aggravate the phenotype of EAE
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In addition, the author also analyzed various physiological parameters related to thermogenesis in the cold-exposed mice.
The results showed that cold exposure improved EAE while not affecting the body's thermogenic response and body temperature stability
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Finally, by detecting the cytokine expression of pathogenic T cells, the authors confirmed that cold exposure improves the EAE phenotype by inhibiting monocyte-mediated activation of autoreactive T cells
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In summary, the work of the research team shows that temperature is a key determinant of the severity of EAE, and cold exposure is an effective stimulus to reduce inflammation in the nervous system
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This discovery not only provides a new understanding of the pathogenic mechanism of nervous system inflammation, but also provides a new method for the prevention and treatment of MS and other autoimmune diseases
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Original link: https://doi.
org/10.
1016/j.
cmet.
2021.
10.
002 Platemaker: 11 References 1.
Buck, MD, Sowell, RT, Kaech, SM, and Pearce, EL (2017).
Metabolic instruction of immunity.
Cell 169, 570–586.
2.
Ajami, B.
, Bennett, JL, Krieger, C.
, McNagny, KM, and Rossi, FM (2011).
Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool.
Nat.
Neurosci.
14, 1142–1149.
3.
Cannon, B.
, and Nedergaard, J.
(2004).
Brown adipose tissue: function and physiological significance.
Physiol.
Rev.
84, 277–359.
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