The Transcription Factor MAZR/PATZ1 Regulates the Development of FOXP3(+) Regulatory T Cells

Forkhead box protein P3+ (FOXP3+) regulatory T cells (Treg cells) play a key role in maintaining tolerance and immune homeostasis. Here, we report that a T cell-specific deletion of the transcription factor MAZR (also known as PATZ1) leads to an increased frequency of T-reg cells, while enforced MAZR expression impairs Treg cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic Treg cell development and during in-vitro-induced human Treg cell differentiation, suggesting that MAZR protein levels are critical for controlling Treg cell development. However, MAZR-deficient T-reg cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral Treg cells. Finally, the loss of MAZR reduces the clinical score in dextran-sodium sulfate (DSS)-induced colitis, suggesting that MAZR activity in T cells controls the extent of intestinal inflammation. Together, these data indicate that MAZR is part of a Treg cell-intrinsic transcriptional network that modulates Treg cell development.</p

Cinnamic Acid Hydrogen Bonds to Isoniazid and N'-(Propan-2-Ylidene)Isonicotinohydrazide, an in situ Reaction Product of Isoniazid and Acetone

A new polymorph of the cinnamic acid-isoniazid cocrystal has been prepared by slow evaporation, namely cinnamic acid-pyridine-4-carbohydrazide (1/1), C9H8O2·C6H7N3O. The crystal structure is characterized by a hydrogen-bonded tetrameric arrangement of two molecules of isoniazid and two of cinnamic acid. Possible modification of the hydrogen bonding was investigated by changing the hydrazide group of isoniazid via an in situ reaction with acetone and cocrystallization with cinnamic acid. In the structure of cinnamic acid-N'-(propan-2-ylidene)isonicotinohydrazide (1/1), C9H8O2·C9H11N3O, carboxylic acid-pyridine O-H···N and hydrazide-hydrazide N-H···O hydrogen bonds are formed

Spontaneous Cocrystal Hydrate Formation in the Solid State: Crystal Structure Aspects and Kinetics

Kinetics of anhydrous cocrystal hydration and that of cocrystal monohydrate formation from starting compounds in the solid state are studied as a function of RH and time. The propensity of the anhydrate to hydration is related to the crystal structures of anhydrous and hydrated forms

Crystal and Molecular Structure and Stability of Isoniazid Cocrystals with Selected Carboxylic Acids

Reaction of isoniazid with benzoic acid, sebacic acid, suberic acid, and cinnamic acid results in formation of cocrystals. Two polymorphs of isoniazid–suberic acid and two polymorphs of isoniazid–cinnamic acid cocrystals were isolated. Crystal structure analysis shows the presence of a pyridine–carboxylic acid synthon in the studied cocrystals. The hydrazide group of isoniazid participates in N–H···O and N–H···N hydrogen bond formation, producing different supramolecular synthons. The stability study of isoniazid cocrystals has been performed over a 22 week period. A comparison of melting points of isoniazid–dicarboxylic acid 2:1 cocrystals shows the decrease of melting point with an increasing length of the acid. Solubility of isoniazid–carboxylic acid cocrystals tends to increase with increasing solubility of the acid

The Effect of pH on Polymorph Formation of the Pharmaceutically Active Compound Tianeptine

The anti-depressant pharmaceutical tianeptine has been investigated to determine the dynamics of polymorph formation under various pH conditions. By varying the pH two crystalline polymorphs were isolated. The molecular and crystal structures have been determined to identify the two polymorphs. One polymorph is an amino carboxylic acid and the other polymorph is a zwitterion. In the solid state the tianeptine moieties are bonded through hydrogen bonds. The zwitterion was found to be less stable and transformed to the acid form. During this investigation an amorphous form was identified

The Transcription Factor MAZR/PATZ1 Regulates the Development of FOXP3 Regulatory T Cells.

Forkhead box protein P3+ (FOXP3+) regulatory T cells (Treg cells) play a key role in maintaining tolerance and immune homeostasis. Here, we report that a T cell-specific deletion of the transcription factor MAZR (also known as PATZ1) leads to an increased frequency of Treg cells, while enforced MAZR expression impairs Treg cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic Treg cell development and during in-vitro-induced human Treg cell differentiation, suggesting that MAZR protein levels are critical for controlling Treg cell development. However, MAZR-deficient Treg cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral Treg cells. Finally, the loss of MAZR reduces the clinical score in dextran-sodium sulfate (DSS)-induced colitis, suggesting that MAZR activity in T cells controls the extent of intestinal inflammation. Together, these data indicate that MAZR is part of a Treg cell-intrinsic transcriptional network that modulates Treg cell development