Abstract

Tobacco smoking is known to impact circulating levels of major immune cells populations, but its effect on specific immune cell subsets remains poorly understood. Here, using high-resolution data from 223 healthy women (25 current and 198 never smokers), we investigated the association between smoking status and 35,651 immune traits capturing immune cell subset frequencies. Our results confirmed that active tobacco smoking is associated with increased frequencies of circulating CD8+ T cells expressing the CD25 activation marker. Moreover, we identified novel associations between smoking status and relative abundances of CD8+ CD25+ memory T cells, CD8+ memory T cells expressing the CCR4 chemokine receptor, and CD4+CD8+ (double-positive) CD25+ T cells. We also observed, in current smokers, a decrease in the relative frequencies of CD4+ T cells expressing the CD38 activation marker and an increase in class-switched memory B cell isotypes IgA, IgG, and IgE. Finally, using data from 135 former female smokers, we showed that the relative frequencies of immune traits associated with active smoking are usually completely restored after smoking cessation, with the exception of subsets of CD8+ and CD8+ memory T cells, which persist partially altered. Our results are consistent with previous findings and provide further evidence on how tobacco smoking shapes leukocyte cell subsets proportion toward chronic inflammation.

Highlights

  • According to the 2019 World Health Organization report, tobacco smoking kills more than eight million people every year [1], and its association with the development of several pathologies, such as respiratory, cardiovascular, neurological, and autoimmune diseases, as well as of several types of cancer, is well established [2,3,4].Immune Traits Associated With Tobacco SmokingIn healthy individuals, tobacco smoking alters leukocyte cells count and distribution in peripheral blood, with several studies showing, in both sexes, an increase in the total number of leukocytes in current smokers compared to former and never smokers [5,6,7]

  • Studies have investigated the effect of tobacco smoking only on primary leukocyte subsets (e.g., T cells, B cells, natural killer cells, monocytes, and granulocytes), showing a decrease in circulating natural killer cells [10], an increase of CD3+ [11], CD4+ [5, 12], memory and naïve T cells [13] in current compared to never smokers

  • We explored the association between selfreported smoking status and 35,651 immune traits measured by flow cytometry in the peripheral blood of 358 healthy women of European ancestry

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Summary

Introduction

Tobacco smoking alters leukocyte cells count and distribution in peripheral blood, with several studies showing, in both sexes, an increase in the total number of leukocytes in current smokers compared to former and never smokers [5,6,7]. The mechanisms underlying this alteration are not fully understood yet, and studies investigating the effect of smoking on the immune system led to conflicting conclusions [8, 9]. A finely detailed investigation of the effect of smoking on more specific leukocyte subsets is still lacking

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