The use of electronic (e)-cigarettes in the long term has been associated with an increased risk of respiratory diseases. Dual use of e-cigarettes and traditional cigarettes may increase these risks even more due to the combined exposure effects of these products. The aim of this study was to investigate the local and systemic effects of e-cigarette use for more than one year and compare them with healthy non-smokers, cigarette smokers, and dual users.
The clinical study was conducted among 22 healthy non-smokers, 20 e-cigarette users, 20 cigarette smokers, and 20 dual users. Participants were matched with age and BMI, had normal baseline lung function, and had no allergies. Exhaled FeNO and bronchial responsiveness were assessed along with reactive oxygen species (ROS), toll-like receptor (TLR) expression, and inflammatory cytokines in blood and sputum.
Exhaled FeNO was higher in e-cigarette users (14 ppb, p = 0.04) and lower in cigarette smokers (9 ppb, p = 0.04) compared to healthy non-smokers (11 ppb). Bronchial responsiveness was increased in e-cigarette users (1.9 mg, p = 0.01) and cigarette smokers (1.9 mg, p = 0.01) compared to healthy non-smokers (2.9 mg). ROS in blood and sputum in e-cigarette users (p = 0.005 and p = 0.04) and dual users (p = 0.003 and p = 0.04) were increased. Also, TLR2 expression in blood granulocytes in all exposed groups (p = 0.001), TLR2 and TLR4 expression in sputum in e-cigarette users (p = 0.04 and p = 0.03) and dual users (p < 0.0001 and p = 0.004) were increased. Moreover, the percentage of IL13 and IFNγ cytokine-producing T cells in blood were increased in e-cigarette users (p = 0.0001 and p < 0.0001) and dual users (p = 0.001 and p < 0.0001).
Our research indicates that both local and systemic inflammatory responses, along with innate immune receptor activity, were significantly altered in e-cigarette users and dual users. Notably, these alterations were detected in e-cigarette users within a short timeframe of just 1 to 3 years of use.
Not applicable.
© 2025. The Author(s).

The human colonic mucosa contains regulatory type 1-like (Tr1-like, i.e., IL-10-secreting and Foxp3-negative) T cells specific for the gut Clostridium Faecalibacterium prausnitzii (F. prausnitzii), which are both decreased in Crohn's disease patients. These data, together with the demonstration, in mice, that colonic regulatory T cells (Treg) induced by Clostridium bacteria are key players in colon homeostasis, support a similar role for F. prausnitzii-specific Treg in the human colon. Here we assessed the mechanisms whereby F. prausnitzii induces human colonic Treg. We demonstrated that F. prausnitzii, but not related Clostridia, skewed human dendritic cells to prime IL-10-secreting T cells. Accordingly, F. prausnitzii induced dendritic cells to express a unique array of potent Tr1/Treg polarizing molecules: IL-10, IL-27, CD39, IDO-1, and PDL-1 and, following TLR4 stimulation, inhibited their up-regulation of costimulation molecules as well as their production of pro-inflammatory cytokines IL-12 (p35 and p40) and TNFα. We further showed that these potent tolerogenic effects relied on F. prausnitzii-induced TLR2/6 triggering, JNK signaling and CD39 ectonucleotidase activity, which was induced by IDO-1 and IL-27. These data, together with the presence of F. prausnitzii-specific Tr1-like Treg in the human colon, point out to dendritic cells polarization by F. prausnitzii as the first described cellular mechanism whereby the microbiota composition may affect human colon homeostasis. Identification of F. prausnitzii-induced mediators involved in Tr1-like Treg induction by dendritic cells opens therapeutic avenues for the treatment of inflammatory bowel diseases.

Immunomodulatory drugs (IMiDs) are effective therapeutics for multiple myeloma (MM), where in different clinical settings they exert their function both directly on MM cells and indirectly by modulating immune cell subsets, although with not completely defined mechanisms. Here we studied the role of IMiDs in the context of autologous hematopoietic stem cell transplantation on the T cell subset distribution in the bone marrow of newly diagnosed MM patients. We found that after transplantation pro-tumor Th17-Th1 and Th22 cells and their related cytokines were lower in patients treated with IMiDs during induction chemotherapy compared to untreated patients. Of note, lower levels of IL-17, IL-22, and related IL-6, TNF-α, IL-1β, and IL-23 in the bone marrow sera correlated with treatment with IMiDs and favorable clinical outcome. Collectively, our results suggest a novel anti-inflammatory role for IMiDs in MM.

Tissue-resident memory T cells (T RM ) persist locally in non-lymphoid tissues where they provide front-line defense against recurring insults. T RM at barrier surfaces express the markers CD103 and/or CD69 which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of T RM nor their ability to re-enter the circulation and potentially migrate to distant tissue sites have been investigated. Using tissue explant cultures, we found that CD4 + CD69 + CD103 + T RM in human skin can downregulate CD69 and exit the tissue. Additionally, we identified a skin-tropic CD4 + CD69 − CD103 + population in human lymph and blood that is transcriptionally, functionally and clonally related to the CD4 + CD69 + CD103 + T RM population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4 + CD103 + T RM population can re-enter circulation, and migrate to secondary human skin sites where they re-assume a T RM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4 + T cell memory in humans. h4>One Sentence Summary/h4> Human CD4 + CD103 + cutaneous resident memory T cells are found in the circulation of healthy subjects, and these cells can seed distant skin sites.

White adipose tissue bridges body organs and plays a fundamental role in host metabolism. To what extent adipose tissue also contributes to immune surveillance and long-term protective defense remains largely unknown. Here, we have shown that at steady state, white adipose tissue contained abundant memory lymphocyte populations. After infection, white adipose tissue accumulated large numbers of pathogen-specific memory T cells, including tissue-resident cells. Memory T cells in white adipose tissue expressed a distinct metabolic profile, and white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge. Induction of recall responses within white adipose tissue was associated with the collapse of lipid metabolism in favor of antimicrobial responses. Our results suggest that white adipose tissue represents a memory T cell reservoir that provides potent and rapid effector memory responses, positioning this compartment as a potential major contributor to immunological memory.
Published by Elsevier Inc.