Three Weeks of Murine Hindlimb Unloading Induces Shifts from B to T and from Th to Tc Splenic Lymphocytes in Absence of Stress and Differentially Reduces Cell-Specific Mitogenic Responses

Gaignier, Fanny; Schenten, Véronique; Bittencourt, Marcelo De Carvalho; Gauquelin‐Koch, Guillemette; Frippiat, Jean-Pol; Legrand-Frossi, Christine

doi:10.1371/journal.pone.0092664

Cited by 53 publications

(52 citation statements)

References 53 publications

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“…While such an exposure may cause stress to the animal, no difference in serum corticostrone levels between experimental and control groups of mice were found, suggesting a low state of stress or adaptation. However, in agreement with our observations regarding CMS exposure, the study found that hindlimb unloading lead to an inversion of the B:T ratio in the spleen [28]. In our study, mice housed in EE-conditions show more accentuated responses upon exposure to stress, such as higher increases in FCM levels, suggesting that these mice were less stressed and thus able to mount a higher HPA axis stress response than mice housed in Cntl-caged environment.…”

Section: Discussionsupporting

confidence: 92%

Enriched environment and stress exposure influence splenic B lymphocyte composition

Gurfein¹,

Hasdemir²,

Milush³

et al. 2017

PLoS ONE

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Prolonged chronic stress has deleterious effects on immune function and is associated with numerous negative health outcomes. The spleen harbors one-fourth of the body’s lymphocytes and mediates both innate and adaptive immune responses. However, the subset of splenic lymphocytes that respond, either adaptively or maladaptively, to various stressors remains largely unknown. Here we investigated the effects of unpredictable chronic mild stress (CMS) exposure on spleen composition in male mice housed in two different caging conditions: standard caging (Cntl) and enriched environment (EE). EE-caged mice exhibited the greatest absolute number of splenocytes and CMS exposure significantly lowered splenocyte numbers in both caging conditions. Glucocorticoid production, measured by mean fecal corticosterone metabolites (FCM), was significantly lower in EE-caged mice vs. Cntl-caged mice. Surprisingly, CMS exposure resulted in an increase in mean FCM in EE-caged mice, but no significant change in Cntl-caged mice. CMS altered the splenic B:T lymphocyte ratio; it reduced the frequency of B cells, but increased the frequency of T cells in EE-caged mice. Splenocyte number and B:T lymphocyte ratio showed a negative relationship with mean FCM. EE-caged mice had a lower frequency of immature and germinal B cells than Cntl-caged mice. CMS markedly increased the frequency of immature and marginal zone B cells, but decreased the frequency of follicular B cells in both caging conditions. Mean FCM correlated positively with frequency of immature, marginal zone and germinal center B cells, but negatively with frequency of follicular B cells. To conclude, splenic immune cells, particularly B lymphocyte composition, are modulated by caging environment and stress and may prime mice differently to respond to immune challenges.

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Section: Discussionsupporting

confidence: 92%

Enriched environment and stress exposure influence splenic B lymphocyte composition

Gurfein¹,

Hasdemir²,

Milush³

et al. 2017

PLoS ONE

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“…Indeed, unlike the detrimental effects of chronic stress, short‐term acute stressors appear to increase immunity (50). As observed in other studies, HU mice had a lower body mass compared with controls (12, 27, 28). Energy intake and expenditure, despite the provision of food in sufficient amounts, is a likely explanation to this observation.…”

Section: Discussionsupporting

confidence: 87%

“…We also studied the evolution of body weight during the experimental period. As noted by others (12,27,28), HU mice lost approximately 10% body weight in the first 2 d and their weight remained below that of controls during the 21 d of HU (Fig. 1B).…”

Section: Kinetics Of Bone Microarchitectural Alterations and Evaluatisupporting

confidence: 83%

Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging

et al. 2014

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Within the bone marrow, the endosteal niche plays a crucial role in B-cell differentiation. Because spaceflight is associated with osteoporosis, we investigated whether changes in bone microstructure induced by a ground-based model of spaceflight, hind limb unloading (HU), could affect B lymphopoiesis. To this end, we analyzed both bone parameters and the frequency of early hematopoietic precursors and cells of the B lineage after 3, 6, 13, and 21 d of HU. We found that limb disuse leads to a decrease in both bone microstructure and the frequency of B-cell progenitors in the bone marrow. Although multipotent hematopoietic progenitors were not affected by HU, a decrease in B lymphopoiesis was observed as of the common lymphoid progenitor (CLP) stage with a major block at the progenitor B (pro-B) to precursor B (pre-B) cell transition (5-to 10-fold decrease). The modifications in B lymphopoiesis were similar to those observed in aged mice and, as with aging, decreased B-cell generation in HU mice was associated with reduced expression of B-cell transcription factors, early B-cell factor (EBF) and Pax5, and an alteration in STAT5-mediated IL-7 signaling. These findings demonstrate that mechanical unloading of hind limbs results in a decrease in early B-cell differentiation resembling age-related modifications in B lymphopoiesis.-Lescale, C., Schenten, V., Djeghloul, D., Bennabi, M., Gaignier, F., Vandamme, K., Strazielle, C., Kuzniak, I., Petite, H., Dosquet, C., Frippiat, J.-P., Goodhardt, M. Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging. FASEB J. 29, 455-463 (2015). www.fasebj.org Key Words: bone remodeling • B-cell differentiation • gravity • immunosenescence HUMAN BIOASTRONAUTIC PROGRAMS have grown during the last 50 yr. Medical and physiologic findings from these missions have demonstrated that spaceflight impacts almost all physiologic systems, including muscle atrophy, bone demineralization, cardiovascular and metabolic dysfunctions, impaired cognitive processes, and reduced immunologic competence. These adaptive responses can affect crew health and performance both in space and upon return to Earth. Indeed, 15 of the 29 Apollo astronauts contracted bacterial or viral infections either during the mission or within a week of returning (1-3). Prolonged exposure to microgravity induces osteopenia, with decreased bone formation and mineralization and increased bone resorption (4, 5), and there are presently no effective countermeasures to mitigate these problems. As a consequence, expanding our knowledge on the effects of longduration spaceflight on crew health and performance is clearly a prerequisite for long-term spaceflight.Immune-competent B and T lymphocytes are derived from hematopoietic stem cells (HSCs) that reside in the bone marrow in specialized niches made up of bone and vascular structures, including bone-forming osteoblasts and bone-resorbing osteoclasts (6). Interactions between HSC and bone marrow niches control the balance be...

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“…Antiorthostatic suspension (AOS) is one of well-known ground based model of simulated microgravity [1]. We could perform AOS experiment by simply hanging the tail of mouse so that the hindlimbs are not bearing weight.…”

Section: Introductionmentioning

confidence: 99%

“…We could perform AOS experiment by simply hanging the tail of mouse so that the hindlimbs are not bearing weight. Using their forelimbs on the ground, animal could move and get food and water [1]. Several researchers have suggested that AOS could reproduce the effect of real microgravity on the cardiovascular, musculoskeletal, and more importantly, immune systems of a living organism [2-4].…”

Section: Introductionmentioning

confidence: 99%

Effect of Long-Term Antiorthostatic Suspension in a Murine Model of Acute Lung Injury

Jang

Jung

Kim

2016

Clin Exp Otorhinolaryngol

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ObjectivesAntiorthostatic suspension (AOS) is ground-based model of simulated microgravity. There is still no study about the effect of long-term microgravity on the clinical course of acute lung injury. We evaluated the effect of simulated microgravity using AOS in a murine model of acute lung injury by lipopolysaccharide (LPS).MethodsThirty BALB/c mice were used. During 4 weeks, mice were equally allocated to control (free movement), restraint (tail suspended, but hindlimbs not unloaded), and AOS group (hindlimb unloaded). After then, mice got intranasal challenge with LPS (20 mg/kg, 50 μL). We measured: weight gain before and after AOS, the number of inflammatory cells and titers of cytokines (interleukin [IL]-1β, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) in bronchoalveolar lavage (BAL) fluid, titer of myeloperoxidase (MPO) in serum and lung homogenate, and histopathologic examination of lung tissue.ResultsAOS group had significant weight loss compared to control and restraint group (P<0.001). AOS group also showed significantly decreased lymphocytes (P=0.023) compared to control group. In AOS group, titer for IL-1β in BAL fluid was significantly lower than restraint group (P=0.049). Titer for serum MPO was significantly decreased in AOS group compared to restraint group (P=0.004). However, there was no significant difference of MPO titers in lung tissue between groups. Histopathologic examination of lung tissue revealed no significant difference in the degree of pulmonary infiltration between restraint and AOS group.ConclusionIn spite of modest anti-inflammatory effect, prolonged AOS caused no significant change in LPS-induced pulmonary inflammation.

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Three Weeks of Murine Hindlimb Unloading Induces Shifts from B to T and from Th to Tc Splenic Lymphocytes in Absence of Stress and Differentially Reduces Cell-Specific Mitogenic Responses

Cited by 53 publications

References 53 publications

Enriched environment and stress exposure influence splenic B lymphocyte composition

Enriched environment and stress exposure influence splenic B lymphocyte composition

Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging

Effect of Long-Term Antiorthostatic Suspension in a Murine Model of Acute Lung Injury

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