Abstract Regulatory B cells (Breg) are vital for inflammation and tissue injury resolution. Here, we investigated the role of transforming growth factor-β1 (TGF-β1)-producing Breg in the murine model of ventilation-induced lung injury (VILI). The percentages of pulmonary CD19highCD44(+) TGF-β1(+) Breg were increased at PV1d and PV10d in VILI mice. Lung injury and inflammation were attenuated by up-regulating TGF-β1 levels with regulation of T-cell immunity. To prolong and stabilize the effect of exogenous TGF-β1, macrophage-derived microvesicles-coated nanoparticles (MNP) loaded TGF-β1(TMNP) were synthesized, and VILI mice were divided into sham, recombinant TGF-β1 (rTGF-β), MNP, and TMNP groups. TMNP increased the TGF-β1 levels in serum and lung tissues at PV10d. Compared with rTGF-β group, lung injury and inflammation in TMNP group at PV1d were attenuated with Breg proliferation; TMNP induced the reduction of pulmonary CD4(+) T cell proportions and CD4(+)/CD8a(+) T cell ratios, but promoted the proliferation of pulmonary CD8a(+) T cells at PV1d and PV10d. Together, TMNP promote the resolution of inflammatory lung injury, which may be associated with the proliferation of Breg to maintain immunological homeostasis.

Most studies of the biological effects of ionizing radiation have been done on a single acute dose, while clinically and environmentally exposures occur under chronic/repetitive conditions. It is important to study effects of different patterns of ionizing radiation. In this study, a rat model was used to compare the effects of repetitive and acute exposure. Groups: (I) control, (II, III) were exposed to fractionated doses (1.5 GyX4) and (2 GyX4), respectively/24h interval, and (IV, V) were exposed to 6 Gy and 8 Gy of whole-body gamma irradiation, respectively. The gene expression of MAPT and tau phosphorylation increased in all irradiated groups but the gene expression of PKN not affected. TGFβ% increased at dose of 2 GyX4 only. In addition, the cell cycle was arrested in S phase. Micronucleus (MN) increased and cell proliferation decreased. In conclusion, the dose and pattern of ionizing radiation do not affect the MAPT and PKN gene expression, but TGF-β, p-tau, MN assay and cell proliferation are significantly affected. The dose of 2 GyX4 showed distinctive effect. Repetitive exposure may increase TGF-β%, which causes radio-resistance and, G2/M delay. Thus, the cell cycle could be regulated in a different manner according to the dose and pattern of irradiation.
© The Author(s) 2022.

The association of autoimmune diseases with particular allellic products of the class-II major histocompatibility complex (MHCII) region implicates the presentation of the offending self-antigens to T cells. Because antigen-presenting cells are tolerogenic when they encounter an antigen under non-inflammatory conditions, the manipulation of antigen presentation may induce antigen-specific tolerance. Here, we show that, in mouse models of experimental autoimmune encephalomyelitis, type 1 diabetes and rheumatoid arthritis, the systemic administration of a single dose of nanobodies that recognize MHCII molecules and conjugated to the relevant self-antigen under non-inflammatory conditions confers long-lasting protection against these diseases. Moreover, co-administration of a nanobody-antigen adduct and the glucocorticoid dexamethasone, conjugated to the nanobody via a cleavable linker, halted the progression of established experimental autoimmune encephalomyelitis in symptomatic mice and alleviated their symptoms. This approach may represent a means of treating autoimmune conditions.
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.