Physiol Rep. 2015 Jul;3(7). doi: 10.14814/phy2.12394.
Cold acclimation affects immune composition in skeletal muscle of healthy lean subjects.
Physiological reports
Anouk A J J van der Lans, Mariëtte R Boon, Mariëlle C Haks, Edwin Quinten, Gert Schaart, Tom H Ottenhoff, Wouter D van Marken Lichtenbelt
Affiliations
Affiliations
- Department of Human Biology, NUTRIM, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
- Department of Human Biology, NUTRIM, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands [email protected].
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
- Department of Human Movement Sciences, NUTRIM, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
PMID: 26149277
PMCID: PMC4552515 DOI: 10.14814/phy2.12394
Abstract
Low environmental temperatures have a profound effect on biological processes in the body, including the immune system. Cold exposure coincides with hormonal changes, which may directly or indirectly alter the immune system, even in the skeletal muscle. The aim of the present study was to investigate the effect of cold acclimation on immune composition in skeletal muscle. Skeletal muscle biopsies were obtained from 17 healthy lean subjects before and after 10 days of mild cold exposure (15 °: C, 6 h/day). Nonshivering thermogenesis was calculated by indirect calorimetry. We found that cold acclimation increased nonshivering thermogenesis from 10.8 ± 7.5 before to 17.8 ± 11.1% after cold acclimation (P < 0.01), but did not affect plasma catecholamine nor cytokine levels. In contrast, cold acclimation affected mRNA expression of several immune cell markers in skeletal muscle. It downregulated expression of the Th17 markers RORC (-28%, P < 0.01) and NEDD4L (-15%, P < 0.05), as well as the regulatory T-cell marker FOXP3 (-13%, P < 0.05). Furthermore, cold acclimation downregulated expression of the M2 macrophage markers CCL22 (-50%, P < 0.05), CXCL13 (-17%, P < 0.05) and CD209 (-15%, P < 0.05), while the M1 macrophage marker IL12B was upregulated (+141%, P < 0.05). Cold acclimation also enhanced several markers related to interferon (IFN) signaling, including TAP1 (+12%, P < 0.01), IFITM1/3 (+11%, P < 0.05), CD274 (+36%, P < 0.05) and STAT 2 (+10%, P < 0.05). In conclusion, 10 days of intermittent cold exposure induces marked changes in the expression of immune cell markers in skeletal muscle of healthy lean subjects. The physiological consequences and therapeutic relevance of these changes remain to be determined.
© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Keywords: Cold acclimation; Th17 cells; macrophages; skeletal muscle; thermogenesis
References
- J Clin Invest. 2013 Aug;123(8):3395-403 - PubMed
- PLoS One. 2014 Oct 22;9(10):e110774 - PubMed
- PLoS One. 2014 Apr 10;9(4):e94698 - PubMed
- Am J Physiol Regul Integr Comp Physiol. 2014 Jul 15;307(2):R103-13 - PubMed
- Can J Physiol Pharmacol. 1998 Sep;76(9):828-36 - PubMed
- Am J Physiol Regul Integr Comp Physiol. 2011 Aug;301(2):R285-96 - PubMed
- Science. 2006 Dec 1;314(5804):1461-3 - PubMed
- Arch Virol. 1996;141(7):1221-9 - PubMed
- Diabetes. 2012 Dec;61(12):3106-13 - PubMed
- Clin Sci (Lond). 2015 Jan;128(2):143-51 - PubMed
- Proc Natl Acad Sci U S A. 2014 May 20;111(20):7379-84 - PubMed
- Nat Immunol. 2007 Apr;8(4):345-50 - PubMed
- Annu Rev Immunol. 2009;27:485-517 - PubMed
- Exp Physiol. 2000 May;85(3):321-6 - PubMed
- J Immunol. 2009 Oct 1;183(7):4792-9 - PubMed
- J Appl Physiol (1985). 1999 Aug;87(2):699-710 - PubMed
- Physiol Rev. 2004 Jan;84(1):277-359 - PubMed
- J Invest Dermatol. 2008 Nov;128(11):2640-5 - PubMed
- Acta Physiol Scand. 1967 Oct-Nov;71(2):140-50 - PubMed
- Arthritis Rheum. 2006 Apr;54(4):1122-31 - PubMed
- Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1300-10 - PubMed
- Nat Chem Biol. 2011 Jun;7(6):351-8 - PubMed
- Genes Immun. 2012 Jan;13(1):71-82 - PubMed
- J Exp Med. 2007 May 14;204(5):1057-69 - PubMed
- N Engl J Med. 2007 Feb 8;356(6):580-92 - PubMed
- Cell Metab. 2011 Aug 3;14(2):272-9 - PubMed
- Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993 Dec;13(12):739-40, 710 - PubMed
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