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Mechanisms of epigenomic and functional convergence between glucocorticoid- and IL4-driven macrophage programming

IL4 and glucocorticoids elicit a homeostatic phenotype in macrophages. Here the authors show that these disparate stimuli yield converging epigenomic and transcriptomic changes, enacted by transcription factors KLF4 and the glucocorticoid receptor, and integrated by their shared coregulator GRIP1.

Dinesh K. Deochand
Marija Dacic
Inez Rogatsky
ResearchOpen Access18 Oct 2024
Nature Communications

Volume: 15, P: 1-18
Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice

Autoimmunity mediated by age-associated B cells (ABC) can affect males and females differently. Here, using a lupus-like mouse model that affects females more severely, the authors observe an ABC mediated and guanine nucleotide exchange factor (GEF) restrained pathogenic process involving TLR7.

Edd Ricker
Michela Manni
Alessandra B. Pernis
ResearchOpen Access10 Aug 2021
Nature Communications

Volume: 12, P: 1-21
Negative elongation factor complex enables macrophage inflammatory responses by controlling anti-inflammatory gene expression

Macrophage activation is integral to innate immunity and inflammation, and involves transcriptome remodeling leading to the rapid upregulation of pro- and anti-inflammatory effector genes. Here the authors show that the negative elongation factor (NELF) complex controls the transcription of anti-inflammatory genes through Pol II pause release.

Li Yu
Bin Zhang
Xiaoyu Hu
ResearchOpen Access08 May 2020
Nature Communications

Volume: 11, P: 1-13
The transcriptional coregulator GRIP1 controls macrophage polarization and metabolic homeostasis

GRIP1 cooperates with the glucocorticoid receptor to repress inflammatory genes. Here the authors show that GRIP1 also controls macrophage polarization, by promoting KLF4-driven activation in response to IL-4, and that mice lacking GRIP1 in macrophages develop severe metabolic dysfunction on a high-fat diet.

Maddalena Coppo
Yurii Chinenov
Inez Rogatsky
ResearchOpen Access28 Jul 2016
Nature Communications

Volume: 7, P: 1-14
Regulation of age-associated B cells by IRF5 in systemic autoimmunity

A unique subset of T-bet-expressing B cells accumulates with aging and in autoimmunity. Pernis and colleagues show that dysregulation of the transcription factor IRF5 occurs after loss of the Rho GTPase–regulatory proteins DEF6 and SWAP-70 and leads to the premature generation of age-associated B cells.

Michela Manni
Sanjay Gupta
Alessandra B. Pernis
Research26 Feb 2018
Nature Immunology

Volume: 19, P: 407-419
Glucocorticoid-induced phosphorylation by CDK9 modulates the coactivator functions of transcriptional cofactor GRIP1 in macrophages

Glucocorticoid reduces inflammation by both inducing anti-inflammatory genes and suppressing pro-inflammatory genes, but how these two functions are dictated is unclear. Here the authors show that phosphorylated glucocorticoid receptor-interacting protein 1 (GRIP1) serves as a coactivator for this response in macrophage.

David A. Rollins
Joubert B. Kharlyngdoh
Inez Rogatsky
ResearchOpen Access23 Nov 2017
Nature Communications

Volume: 8, P: 1-15
The mTORC1-4E-BP-eIF4E axis controls de novo Bcl6 protein synthesis in T cells and systemic autoimmunity

Excessive expansion of the T follicular helper (T_FH) cell pool is associated with autoimmune disease and Def6 has been identified as an SLE risk variant. Here the authors show that Def6 limits proliferation of T_FH cells in mice via alteration of mTORC1 signaling and inhibition of Bcl6 expression.

Woelsung Yi
Sanjay Gupta
Alessandra B. Pernis
ResearchOpen Access15 Aug 2017
Nature Communications

Volume: 8, P: 1-14
In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis

Habib Zahir
Bijan Dehghani
Miguel Otero
ResearchOpen Access01 Jun 2021
Scientific Reports

Volume: 11, P: 1-13
Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity

Yurii Chinenov
Tom K Kerppola
Reviews30 Apr 2001
Oncogene

Volume: 20, P: 2438-2452

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