Role of NF-kappaB2-p100 in regulatory T cell homeostasis and activation

Dhar, Atika; Chawla, M. L.; Chattopadhyay, Somdeb; Oswal, Neelam; Umar, Danish; Gupta, Suman; Bal, Vineeta; Rath, Satyajit; George, Anna; Arimbasseri, Aneeshkumar G.; Basak, Soumen

doi:10.1038/s41598-019-50454-z

Cited by 15 publications

(8 citation statements)

References 80 publications

(135 reference statements)

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“…Nfkb2 signaling in the hematopoietic compartment curtails the generation of Treg cells (Dhar et al, 2019; Grinberg-Bleyer et al, 2018), while our global Nfkb2 −/− mice displayed an increased frequency of Tregs in the colitogenic gut. Therefore, we further examined reciprocal bone marrow chimeras generated using WT and Nfkb2 −/− mice for dissecting the hematopoietic and the stromal Nfkb2 functions in experimental colitis.…”

Section: Resultsmentioning

confidence: 73%

An epithelialNfkb2pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module

Chawla

Mukherjee

Deka

et al. 2020

Preprint

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Aberrant inflammation associated with human ailments, including inflammatory bowel disease (IBD), is typically fuelled by the inordinate activity of RelA/NF-κB transcription factors. As such, the canonical NF-κB module mediates controlled nuclear activation of RelA dimers from the latent cytoplasmic complexes. What provokes pathological RelA activity in the colitogenic gut remains unclear. The noncanonical NF-κB pathway promotes immune organogenesis involving Nfkb2 gene products. Because NF-κB pathways are intertwined, we asked if noncanonical signaling aggravated inflammatory RelA activity. Our investigation revealed frequent engagement of the noncanonical pathway in human IBD. In a mouse model, an Nfkb2 function exacerbated gut inflammation by amplifying the epithelial RelA activity induced upon intestinal injury. Our mechanistic studies clarified that cell-autonomous Nfkb2 signaling supplemented latent NF-κB dimers leading to hyperactive canonical RelA response in the inflamed colon. In sum, regulation of latent NF-κB dimers links noncanonical signaling to RelA-driven inflammatory pathologies and may provide for therapeutic targets.

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Section: Resultsmentioning

confidence: 73%

An epithelialNfkb2pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module

Chawla

Mukherjee

Deka

et al. 2020

Preprint

Self Cite

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“…Deleterious mutations in RelB result in patients with combined immunodeficiency and autoimmunity, and RelB absence alters T cell maturation in the thymus to cause the autoimmune features in humans 41 . NF-κB1-RelB dimers contribute to regulatory T cells activation 42 , and regulatory T cells from the thymus improve maternal tolerance to the fetus in pregnancy 14 . RelB plays an essential role in the medullary thymic epithelial cell development, which control T-cell tolerance 43 , but disruption of RelB is related with multiorgan inflammation and hematopoietic abnormalities in mice 44 .…”

Section: Discussionmentioning

confidence: 99%

Changes in expression of nuclear factor kappa B subunits in the ovine thymus during early pregnancy

Yang

Cai

Fang

et al. 2022

Sci Rep

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There is a pregnant maternal immunological tolerance that protects the fetus and promotes its growth, and nuclear factor kappa B (NF-κB) family participates in the regulation of innate immune and adaptive immune responses. The thymus is related to establishing central tolerance, and early pregnancy has effects on expression of a good number of genes and proteins in the maternal thymus in sheep. However, it is unclear whether early pregnancy changes expression of NF-κB subunits in the ovine thymus. In this study, the thymic samples were collected from day 16 of non-pregnant ewes, and days 13, 16 and 25 of pregnant ewes, and the expression of NF-κB members (NF-κB1, NF-κB2, RelA, RelB and c-Rel) was analyzed through real-time quantitative PCR, Western blot and immunohistochemical analysis. The results showed that c-Rel mRNA and protein upregulated at day 25 of pregnancy, and NF-κB1 mRNA and proteins increased at days 16 and 25 of pregnancy, and RelB mRNA and proteins enhanced during early pregnancy. However, expression levels of NF-κB2 and RelA were decreased during early pregnancy, but upregulated from day 13 to 25 of pregnancy. In addition, the RelA protein was located in the epithelial reticular cells, capillaries and thymic corpuscles. This paper reported for the first time that early pregnancy induced expression of NF-κB1, RelB and c-Rel, but inhibited expression of NF-κB2 and RelA in the maternal thymus during early pregnancy, which is involved in the central immune tolerance, and helpful for successful pregnancy in sheep.

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“…Deleterious mutations in RelB result in patients with combined immunode ciency and autoimmunity, and RelB absence alters T cell maturation in the thymus to cause the autoimmune features in humans 40 . NF-κB1-RelB dimers contribute to regulatory T cells activation 41 , and regulatory T cells from the thymus improve maternal tolerance to the fetus in pregnancy 14 . Therefore, the upregulation of RelB and NF-κB1 in the maternal thymus may be associated with regulatory T cells activation, which is helpful for normal pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Changes in expression of nuclear factor kappa B subunits in the ovine thymus during early pregnancy

Yang

Cai

Fang

et al. 2022

Preprint

View full text Add to dashboard Cite

There is pregnant maternal immunological tolerance that protects the fetus and promotes its growth, and nuclear factor kappa B (NF-κB) family participates in the regulation of innate immune and adaptive immune responses. The thymus is related to establishing central tolerance, and early pregnancy has effects on expression of a good number of genes and proteins in the maternal thymus in sheep. However, it is unclear if early pregnancy changes expression of NF-κB subunits in the ovine thymus. In this study, the thymic samples were collected from day 16 of non-pregnant ewes, and days 13, 16 and 25 of pregnant ewes, and the expression of NF-κB members (NF-κB1, NF-κB2, RelA, RelB and c-Rel) were analyzed through real-time quantitative PCR, Western blot and immunohistochemical analysis. The results showed that c-Rel mRNA and protein upregulated at day 25 of pregnancy, and NF-κB1 mRNA and proteins increased at days 16 and 25 of pregnancy, and RelB mRNA and proteins enhanced during early pregnancy. However, expression of NF-κB2 and RelA was decreased during early pregnancy, but upregulated from day 13 to 25 of pregnancy. In addition, the RelA protein was located in the epithelial reticular cells, capillaries and thymic corpuscles. This paper reported for the first time that early pregnancy induced expression of NF-κB1, RelB and c-Rel, but inhibited expression of NF-κB2 and RelA in the maternal thymus during early pregnancy, which is involved in the central immune tolerance, and helpful for successful pregnancy in sheep.

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Role of NF-kappaB2-p100 in regulatory T cell homeostasis and activation

Cited by 15 publications

References 80 publications

An epithelialNfkb2pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module

An epithelialNfkb2pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module

Changes in expression of nuclear factor kappa B subunits in the ovine thymus during early pregnancy

Changes in expression of nuclear factor kappa B subunits in the ovine thymus during early pregnancy

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