Antigen-induced immune suppression, like T cell activation, requires antigen-presenting cells (APCs); however, the role of APCs in mediating these opposing effects is not well understood, especially in vivo. We report that genetic inactivation of CD11b, which is a CD18 subfamily of integrin receptors that is highly expressed on APCs, abolishes orally induced peripheral immune tolerance (oral tolerance) without compromising APC maturation or antigen-specific immune activation. The defective oral tolerance in CD11b−/− mice can be restored by adoptive transfer of wild-type APCs. CD11b deficiency leads to enhanced interleukin (IL) 6 production by APCs, which subsequently promotes preferential differentiation of naive T cells to T helper 17 (Th17) cells, which are a T cell lineage characterized by their production of IL-17. Consequently, antigen feeding and immunization of CD11b−/− mice results in significant production of IL-17 within the draining lymph nodes that interferes with the establishment of oral tolerance. Together, we conclude that CD11b facilitates oral tolerance by suppressing Th17 immune differentiation.

ObjectiveAlthough physical therapy can help preserve mobility in patients with systemic sclerosis (SSc), stretching has not been used systematically as a treatment to prevent or reverse the disease process. We previously showed in rodent models that stretching promotes the resolution of connective tissue inflammation and reduces new collagen formation after injury. Here, we tested the hypothesis that stretching would impact scleroderma development using a mouse sclerodermatous graft-versus-host disease (sclGvHD) model.MethodsThe model consists in the adoptive transfer (allogeneic) of splenocytes from B10.D2 mice (graft) into Rag2−/− BALB/c hosts (sclGvHD), resulting in skin inflammation followed by fibrosis over 4 weeks. SclGvHD mice and controls were randomized to stretching in vivo for 10 min daily versus no stretching.ResultsWeekly ultrasound measurements of skin thickness and subcutaneous tissue mobility in the back (relative tissue displacement during passive trunk motion) successfully captured the different phases of the sclGvHD model. Stretching reduced skin thickness and increased subcutaneous tissue mobility compared to no stretching at week 3. Stretching also reduced the expression of CCL2 and ADAM8 in the skin at week 4, which are two genes known to be upregulated in both murine sclGvHD and the inflammatory subset of human SSc. However, there was no evidence that stretching attenuated inflammation at week 2.ConclusionDaily stretching for 10 min can improve skin thickness and mobility in the absence of any other treatment in the sclGvHD murine model. These pre-clinical results suggest that a systematic investigation of stretching as a therapeutic modality is warranted in patients with SSc.

An obvious consequence of the coronavirus disease (COVID-19) pandemic is the worldwide reduction in social interaction, which is associated with many adverse effects on health in humans from babies to adults. Although social development under normal or isolated environments has been studied since the 1940s, the mechanism underlying social isolation (SI)-induced brain dysfunction remains poorly understood, possibly due to the complexity of SI in humans and translational gaps in findings from animal models. Herein, we present a systematic review that focused on brain changes at the molecular, cellular, structural and functional levels induced by SI at different ages and in different animal models. SI studies in humans and animal models revealed common socioemotional and cognitive deficits caused by SI in early life and an increased occurrence of depression and anxiety induced by SI during later stages of life. Altered neurotransmission and neural circuitry as well as abnormal development and function of glial cells in specific brain regions may contribute to the abnormal emotions and behaviors induced by SI. We highlight distinct alterations in oligodendrocyte progenitor cell differentiation and oligodendrocyte maturation caused by SI in early life and later stages of life, respectively, which may affect neural circuit formation and function and result in diverse brain dysfunctions. To further bridge animal and human SI studies, we propose alternative animal models with brain structures and complex social behaviors similar to those of humans.