Publications by authors named "Mihir Pendse"

5 Publications

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Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation.

Nat Immunol 2020 04 16;21(4):422-433. Epub 2020 Mar 16.

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20's OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20 mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions. A20 cells exhibited prolonged IκB kinase activity that drove exaggerated transcription of late-phase nuclear factor-κB response genes in vitro and in prediseased mouse paws in vivo. In addition, mice expressing double-mutant A20 proteins in A20's ZF4 and ZF7 motifs died perinatally with multi-organ inflammation. Therefore, A20's ZF4 and ZF7 motifs synergistically prevent inflammatory disease in a non-catalytic manner.
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http://dx.doi.org/10.1038/s41590-020-0634-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195210PMC
April 2020

Epithelial retinoic acid receptor β regulates serum amyloid A expression and vitamin A-dependent intestinal immunity.

Proc Natl Acad Sci U S A 2019 05 16;116(22):10911-10916. Epub 2019 May 16.

Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390;

Vitamin A is a dietary component that is essential for the development of intestinal immunity. Vitamin A is absorbed and converted to its bioactive derivatives retinol and retinoic acid by the intestinal epithelium, yet little is known about how epithelial cells regulate vitamin A-dependent intestinal immunity. Here we show that epithelial cell expression of the transcription factor retinoic acid receptor β (RARβ) is essential for vitamin A-dependent intestinal immunity. Epithelial RARβ activated vitamin A-dependent expression of serum amyloid A (SAA) proteins by binding directly to promoters. In accordance with the known role of SAAs in regulating Th17 cell effector function, epithelial RARβ promoted IL-17 production by intestinal Th17 cells. More broadly, epithelial RARβ was required for the development of key vitamin A-dependent adaptive immune responses, including CD4 T-cell homing to the intestine and the development of IgA-producing intestinal B cells. Our findings provide insight into how the intestinal epithelium senses dietary vitamin A status to regulate adaptive immunity, and highlight the role of epithelial cells in regulating intestinal immunity in response to diet.
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http://dx.doi.org/10.1073/pnas.1812069116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561173PMC
May 2019

IMPULSE: A scalable algorithm for design of minimum specific absorption rate parallel transmit RF pulses.

Magn Reson Med 2019 04 13;81(4):2808-2822. Epub 2018 Nov 13.

Stanford University, Department of Radiology, Stanford, California.

Purpose: Managing local specific absorption rate (SAR) in parallel transmission requires ensuring that the peak SAR over a large number of voxels (> ) is below the regulatory limit. The safety risk to the patient depends on cumulative (not instantaneous) SAR thus making a joint design of all RF pulses in a sequence desirable. We propose the Iterative Minimization Procedure with Uncompressed Local SAR Estimate (IMPULSE), an efficient optimization formulation and algorithm that can handle uncompressed SAR matrices and optimize pulses for all slices jointly within a practical time frame.

Theory And Methods: IMPULSE optimizes parallel transmit pulses for small-tip-angle slice selective excitation to minimize a single cost function incorporating multiple quantities (local SAR, global SAR, and per-channel power) averaged over the entire multislice scan subject to a strict constraint on excitation accuracy. Pulses for an 8-channel 7T head coil were designed with IMPULSE and compared with pulses designed using generic optimization algorithms and VOPs to assess the computation time and SAR performance benefits.

Results: IMPULSE achieves lower SAR and shorter computation time compared with a VOP approach. Compared with the generic sequential quadratic programming algorithm, computation time is reduced by a factor of 5-6 by using IMPULSE. Using as many as 6 million local SAR terms, up to 120 slices can be designed jointly with IMPULSE within 45 s.

Conclusions: IMPULSE can handle significantly larger number of SAR matrices and slices than conventional optimization algorithms, enabling the use of uncompressed or partially compressed SAR matrices to design pulses for a multislice scan in a practical time frame.
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http://dx.doi.org/10.1002/mrm.27589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372346PMC
April 2019

Paneth cells secrete lysozyme via secretory autophagy during bacterial infection of the intestine.

Science 2017 09 27;357(6355):1047-1052. Epub 2017 Jul 27.

Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Intestinal Paneth cells limit bacterial invasion by secreting antimicrobial proteins, including lysozyme. However, invasive pathogens can disrupt the Golgi apparatus, interfering with secretion and compromising intestinal antimicrobial defense. Here we show that during bacterial infection, lysozyme is rerouted via secretory autophagy, an autophagy-based alternative secretion pathway. Secretory autophagy was triggered in Paneth cells by bacteria-induced endoplasmic reticulum (ER) stress, required extrinsic signals from innate lymphoid cells, and limited bacterial dissemination. Secretory autophagy was disrupted in Paneth cells of mice harboring a mutation in autophagy gene that confers increased risk for Crohn's disease in humans. Our findings identify a role for secretory autophagy in intestinal defense and suggest why Crohn's disease is associated with genetic mutations that affect both the ER stress response and autophagy.
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http://dx.doi.org/10.1126/science.aal4677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702267PMC
September 2017

Immunology: Mum's microbes boost baby's immunity.

Nature 2016 May 27;533(7601):42-3. Epub 2016 Apr 27.

Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

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http://dx.doi.org/10.1038/nature17895DOI Listing
May 2016