Journal: Frontiers in Immunology

Article Title: Induction of T cell exhaustion by JAK1/3 inhibition in the treatment of alopecia areata

doi: 10.3389/fimmu.2022.955038

Figure Lengend Snippet: γc cytokines regulated effector T cell exhaustion. (A) to (J) T cells from C3H/HeJ mice without AA were stimulated with 500 ng/ml anti-CD3 in the presence of indicated regents in vitro for 4 (d) (A) and (B) The expression of PD-1 on CD8 + T cells was measured by FACS after treated with increasing dose of Ifidancitinib. *P < 0.05, ***P < 0.001 (one-way ANOVA). (C) and (D) The expression of PD-1 on CD8 + T cells was measured by FACS after treated with increasing dose of STAT5 inhibitor. *P < 0.05, ***P < 0.001 (one-way ANOVA). (E) and (F) The expression of PD-1 on CD8 + T cells was measured by FACS after treated with 1 µM of JAK1i (Itacitinib), JAK2i (Fedratinib), JAK3i (Ritlecitinib), JAK1/2-selective inhibitor Ruxolitinib (Ruxo), or pan-JAK inhibitor Tofacitinib (Tofa). ns indicates not significant, *P < 0.05, ***P < 0.001. P values were determined using one-way ANOVA followed by Brown-Forsythe test. (G) and (H) The expression of PD-1 on CD8 + T cells was measured by FACS after treated with 20 µg/ml IL-2 neutralizing mAbs. **P < 0.01. (Unpaired Student t test). (I) The expression of Eomes and TOX in CD8 + T cells was measured by FACS after treated with 1µM of JAK1i (Itacitinib), JAK2i (Fedratinib), JAK3i (Ritlecitinib), JAK1/2-selective inhibitor Ruxolitinib (Ruxo), Ifidancitinib, or pan-JAK inhibitor Tofacitinib (Tofa). (J) The expression of Eomes and TOX in CD8 + T cells was measured by FACS after treated with 20 µg/ml IL-2 neutralizing mAbs and isotype control mAbs. (K) to (M) C3H/HeJ mice with AA were treated with a combination of IL-2 neutralizing mAbs, IL-9 neutralizing mAbs and IL-15 neutralizing mAbs or isotype for 8 weeks. (K) Representative images of anti-IL2/9/15 or isotype treated C3H/HeJ mice before or after 8 weeks treatment. (L) Percentage of skin hair loss or regrowth is shown before and after treatment. **P < 0.01, ***P < 0.001 (Unpaired Student t test). The expression of PD-1 on CD8+ T cells was measured by FACS after treated with 20 µg/ml IL-2/9/15 neutralizing mAbs. **P < 0.01. (Unpaired Student t test). The results are representative of two separate experiments. (N) to (P) C3H/HeJ mice with AA were treated with Ritlecitinib or vehicle systemically for 8 weeks. (N) Representative images of Ritlecitinib or vehicle treated C3H/HeJ mice before or after 8 weeks treatment. (O) Percentage of skin hair loss or regrowth is shown before and after treatment. ***P < 0.001 (Unpaired Student t test). (P) The frequency of PD-1+TOX+CD44+CD8+ T cells within SDLNs were measured with mice that were systemically treated with Ritlecitinib or vehicle for 8 weeks. *P < 0.05. (Unpaired Student t test). The results are representative of two separate experiments. The results are representative of two separate experiments.

Article Snippet: Itacitinib (catalog HY-16997, MedChemExpress), Fedratinib (catalog 202893, Medkoo), Ritlecitinib (catalog PZ0316, MilliporeSigma), Ruxolitinib (catalog S1378, Selleck), Tofacitinib (catalog 200811, Medkoo)

Techniques: In Vitro, Expressing, Control

Journal: Arthritis research & therapy

Article Title: Suberosin attenuates rheumatoid arthritis by repolarizing macrophages and inhibiting synovitis via the JAK/STAT signaling pathway.

doi: 10.1186/s13075-025-03481-3

Figure Lengend Snippet: Fig. 6 SBR modulates the JAK/STAT pathway activation in BMDMs. (A) Representative western blots of JAK1 and STAT3 phosphorylation levels in BMDMs stimulated with LPS + IFN-γ. (B) Representative western blots of JAK1 and STAT6 phosphorylation levels in BMDMs stimulated with IL-4. (C-D) Quantita tive analysis of p-JAK1/JAK1, p-STAT3/STAT3, and p-STAT6/STAT6 levels in BMDMs. (E) The expression levels of the M1-related genes iNOS and IL-6 in M1 macrophage after treated with Itacitinib or S3I-201 in the presence or absence of SBR for 24 h. (F) The expression levels of the M2-related genes Arg1 and CD206 in M2 macrophage after treated with Itacitinib or AS1517499 in the presence or absence of SBR for 24 h. (G) The levels of TNF-α and IL-6 in M1 macrophage, the level of IL-10 in M2 macrophage using ELISA. Data are presented as the mean ± SD, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

Article Snippet: Cells were treated with 20μM Itacitinib (SelleckChem, USA), 100 μM STAT3 inhibitor (S3I-201) (SelleckChem) or 10 μM STAT6 inhibitor (AS1517499) (SelleckChem).

Techniques: Activation Assay, Western Blot, Phospho-proteomics, Expressing, Enzyme-linked Immunosorbent Assay

Journal: Journal for Immunotherapy of Cancer

Article Title: Exploring the safety, effect on the tumor microenvironment, and efficacy of itacitinib in combination with epacadostat or parsaclisib in advanced solid tumors: a phase I study

doi: 10.1136/jitc-2021-004223

Figure Lengend Snippet: Study design. *Group A included three dose levels: itacitinib 300 mg once a day plus epacadostat 50 mg two times per day, itacitinib 300 mg once a day plus epacadostat 100 mg two times per day, and itacitinib 300 mg once a day plus epacadostat 300 mg two times per day. †Treatment for groups A-1 and A-2 was itacitinib 300 mg once a day plus epacadostat 300 mg two times per day. ‡Group B included seven dose levels: itacitinib 300 mg once a day plus parsaclisib 2.5 mg once every other day, itacitinib 300 mg once a day plus parsaclisib 5 mg once a day, itacitinib 300 mg once a day plus parsaclisib 10 mg once a day, itacitinib 100 mg once a day plus parsaclisib 0.3 mg once a day, itacitinib 100 mg once a day plus parsaclisib 1 mg once a day, itacitinib 300 mg once a day plus parsaclisib 0.3 mg once a day, and itacitinib 300 mg once a day plus parsaclisib 1 mg once a day. §Treatment for groups B-1 and B-2 was itacitinib 300 mg once a day plus parsaclisib 10 mg once a day. ¶Treatment for groups B-3 and B-5 was itacitinib 100 mg once a day plus parsaclisib 0.3 mg once a day. ǁTreatment for group B-4 was parsaclisib 0.3 mg once a day monotherapy; one patient in group B-4 had itacitinib 100 mg once a day added, per protocol, due to disease progression. All patients receiving parsaclisib plus itacitinib (except parsaclisib 0.3 mg once a day plus itacitinib 100 mg once a day) were required to receive a standard Pneumocystis jirovecii prophylaxis regimen determined by the investigator. BID, two times per day; GU, genitourinary; HNSCC, head and neck squamous cell carcinoma; MTD, maximum tolerated dose; NSCLC, non-small cell lung cancer; PAD, pharmacologically active dose; PD-1, programmed cell death-1; QD, once a day; QoD, once every other day; TCC, transitional cell carcinoma.

Article Snippet: Prior PK analysis demonstrated that itacitinib could be administered with epacadostat or parsaclisib, as concomitant administration of itacitinib did not affect the PK profile of either epacadostat or parsaclisib, or vice versa (data on file, Incyte).

Techniques:

Journal: Journal for Immunotherapy of Cancer

Article Title: Exploring the safety, effect on the tumor microenvironment, and efficacy of itacitinib in combination with epacadostat or parsaclisib in advanced solid tumors: a phase I study

doi: 10.1136/jitc-2021-004223

Figure Lengend Snippet: Immunohistochemistry analysis of T cell infiltration in (A) itacitinib plus epacadostat treatment samples (n=12), (B) itacitinib plus high-dose parsaclisib (1–10 mg) treatment samples (n=9; only 8 samples were available for TIL response assessment, since 1 sample failed FoxP3 analysis), and (C) itacitinib plus low-dose parsaclisib (0.3 mg) treatment samples (n=12). Comparisons were performed using Wilcoxon matched-pairs signed-rank test; changes were deemed significant at p<0.05. TIL responder was defined as ≥50% increase in the CD8 + to FoxP3 + cell ratio in the tumor compartment post-treatment versus baseline, as determined by immunohistochemistry. FoxP3, forkhead box protein 3; NS, not significant; TIL, tumor-infiltrating lymphocyte.

Article Snippet: Prior PK analysis demonstrated that itacitinib could be administered with epacadostat or parsaclisib, as concomitant administration of itacitinib did not affect the PK profile of either epacadostat or parsaclisib, or vice versa (data on file, Incyte).

Techniques: Immunohistochemistry

Journal: Journal for Immunotherapy of Cancer

Article Title: Exploring the safety, effect on the tumor microenvironment, and efficacy of itacitinib in combination with epacadostat or parsaclisib in advanced solid tumors: a phase I study

doi: 10.1136/jitc-2021-004223

Figure Lengend Snippet: Plasma proteins differentially expressed with itacitinib plus epacadostat or parsaclisib treatment

Article Snippet: Prior PK analysis demonstrated that itacitinib could be administered with epacadostat or parsaclisib, as concomitant administration of itacitinib did not affect the PK profile of either epacadostat or parsaclisib, or vice versa (data on file, Incyte).

Techniques: Binding Assay, Activation Assay

Journal: Pharmacological Research

Article Title: The new entries in the therapeutic armamentarium: The small molecule JAK inhibitors

doi: 10.1016/j.phrs.2019.104392

Figure Lengend Snippet: JAK inhibitors in early development and those that have been discontinued.

Article Snippet: Itacitinib (INCB039110) , Incyte , JAK1/JAK2 , II , RA , NCT01626573 , Discontinued.

Techniques: