Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

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Mucosal-associated invariant T cells in Giant Cell Arteritis

Journal of Autoimmunity ◽

10.1016/j.jaut.2021.102652 ◽

2021 ◽

Vol 121 ◽

pp. 102652

Author(s):

Thibault Ghesquière ◽

Marion Ciudad ◽

André Ramon ◽

Hélène Greigert ◽

Claire Gerard ◽

...

Keyword(s):

T Cells ◽

Giant Cell Arteritis ◽

Giant Cell ◽

Invariant T Cells

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P32: Mucosal‐associated invariant T cells and interleukin‐17 lineage in hidradenitis suppurativa

British Journal of Dermatology ◽

10.1111/bjd.19998 ◽

2021 ◽

Vol 185 (S1) ◽

pp. 40-40

Keyword(s):

T Cells ◽

Hidradenitis Suppurativa ◽

Interleukin 17 ◽

Invariant T Cells

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THU0051 LOW-DOSE INTERLEUKIN-2 SELECTIVELY EXPAND AND ACTIVATE REGULATORY T CELLS ACROSS 13 AUTOIMMUNE DISEASES.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2743 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 237.1-238

Author(s):

M. Rosenzwajg ◽

R. Lorenzon ◽

P. Cacoub ◽

F. Pitoiset ◽

S. Aractingi ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Autoimmune Diseases ◽

Inflammatory Disease ◽

Low Dose ◽

Therapeutic Potential ◽

Interleukin 2 ◽

Clinical Effects ◽

Research Support ◽

Open Label

Background:Regulatory T cells (Tregs) prevent autoimmunity and control inflammation. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential for any autoimmune or inflammatory disease (AIID). We performed a disease-finding “basket trial” (TRANSREGNCT01988506) in patients affected by one of 11 different AIID and reported the outcome of the first 46 patients (Rosenzwajg et al, ARD 2019).Objectives:Here we analyzed and discussed results from deep immunophenotyping, of 78 patients, to comprehensively study the effect of ld-IL2 on the immune system of patients affected by various AIIDMethods:We performed a prospective, open label, phase I-IIa study in 78 patients with a mild to moderate form of one of 13 selected AIID. All patients received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Deep immunophenotyping was performed before and after 5 days of ld-IL2.Results:ld-IL2 significantly expands both memory Tregs as well as naïve Tregs, including recent thymic emigrant Tregs. It also activates Tregs as demonstrated by the significantly increased expression of HLA-DR, CD39, CD73, GITR, CTLA-4. Similar results were observed across the different AIID.Conclusion:ld-IL2 “universally” improves Treg fitness across 13 autoimmune and inflammatory disease.References:[1]Rosenzwajg M#, Lorenzon R#, Cacoub P, Pham HP, Pitoiset F, El Soufi K, RIbet C, Bernard C, Aractingi S, Banneville B, Beaugerie L, Berenbaum F, Champey J, Chazouilleres O, Corpechot C, Fautrel B, Mekinian A, Regnier E, Saadoun D, Salem JE, Sellam J, Seksik P, Daguenel-Nguyen A, Doppler V, Mariau J, Vicaut E, Klatzmann D. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 2019 Feb;78(2):209-217. doi: 10.1136/annrheumdis-2018-214229. Epub 2018 Nov 24.Disclosure of Interests:Michelle Rosenzwajg: None declared, Roberta Lorenzon: None declared, Patrice cacoub: None declared, Fabien Pitoiset: None declared, Selim Aractingi: None declared, Beatrice Banneville Speakers bureau: Lilly, Novartis, Laurent Beaugerie: None declared, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Julien Champey: None declared, Olivier Chazouilleres: None declared, Christophe Corpechot: None declared, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Arsene Mekinian: None declared, Elodie Regnier: None declared, david Saadoun: None declared, Joe-Elie Salem: None declared, Jérémie SELLAM: None declared, Philippe Seksik: None declared, David Klatzmann Consultant of: ILTOO Pharma

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Chronic stress physically spares but functionally impairs innate-like invariant T cells

Cell Reports ◽

10.1016/j.celrep.2021.108979 ◽

2021 ◽

Vol 35 (2) ◽

pp. 108979

Author(s):

Patrick T. Rudak ◽

Joshua Choi ◽

Katie M. Parkins ◽

Kelly L. Summers ◽

Dwayne N. Jackson ◽

...

Keyword(s):

T Cells ◽

Chronic Stress ◽

Invariant T Cells

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Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology

Science Advances ◽

10.1126/sciadv.abe4601 ◽

2021 ◽

Vol 7 (21) ◽

pp. eabe4601

Author(s):

Sandro Da Mesquita ◽

Jasmin Herz ◽

Morgan Wall ◽

Taitea Dykstra ◽

Kalil Alves de Lima ◽

...

Keyword(s):

T Cells ◽

Cognitive Decline ◽

Brain Aging ◽

Therapeutic Potential ◽

T Cell Response ◽

Age Related ◽

Lymphatic Vasculature ◽

Amyloid Aβ ◽

Β Amyloid ◽

Old Mice

Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)–dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer’s disease–like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases.

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