Elevated peripheral frequencies of Th22 cells: a novel potent participant in obesity and type 2 diabetes.
OBJECTIVE
Chronic low-grade inflammation has long been recognized as the central link between obesity and type 2 diabetes (T2D). The novel subset of T helper (Th) cells, Th22, plays an emerging role in chronic inflammation. We investigated the potential association between Th22 and the pathogenesis of obesity and T2D.


METHODS
Ninety T2D inpatients (T2D group), 30 healthy participants with BMI ranged from 19 to 23.9 kg/m2 (CTL group) and 30 metabolically healthy obese controls with BMI ≥ 30 kg/m2 (MHO group) were employed in our study. Peripheral frequencies of Th22 and Th1 and Th17 cells were determined by flow cytometry based on their specific cytokine patterns. Cytokine levels in fresh plasma were quantified by ELISA.


RESULTS
Compared to that in CTL group (1.18±0.06%, n = 28), peripheral frequency of Th22 cells was significantly increased in MHO group (1.88±0.10%, n = 30) and in T2D group (2.247±0.10%, n = 89). There was a consistent notable increase in plasma interleukin (IL)-22 of T2D patients [47.56 (30.55-76.89) pg/mL] as compared with that of MHO group [36.65 (29.52-55.70) pg/ml; *P<0.0001] and CTLs [36.33 (31.93-40.62) pg/mL; *P<0.0001]. Furthermore, other than Th1/Th17, previously frequently described participants in obesity and T2D, there was a strong correlation between Th22 frequency and the homeostasis model of assessment for insulin resistance index (r = 0.6771, *P<0.0001) and HOMA for β-cell function (r = -0.7264, *P<0.0001).


CONCLUSIONS
There were increased Th22 frequencies and IL-22 levels in obesity and T2D. Elevated Th22 and IL-22 also aided in the differentiation of MHO from T2D patients. The notable correlation implied that Th22 might play a more determinant role in both insulin resistance and β-cell impairment.
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China ; Institute of Endocrinology and Metabolism, Shandong University, Jinan, China ; Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China.
Ruxing
R
Zhao
Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China.
Dongqi
D
Tang
Centre for Transplant and Renal Research, Westmead Millennium Institute, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia.
Shounan
S
Yi
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China.
Wenjuan
W
Li
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China.
Chuanlong
C
Wu
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China.
Yiran
Y
Lu
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China.
Xinguo
X
Hou
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China.
Jun
J
Song
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China.
Peng
P
Lin
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China ; Institute of Endocrinology and Metabolism, Shandong University, Jinan, China.
Li
L
Chen
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China ; Institute of Endocrinology and Metabolism, Shandong University, Jinan, China.
Lei
L
Sun
D000328:Adult; D016022:Case-Control Studies; D016764:Cell Polarity; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000453:epidemiology / Q000276:immunology*; D010641:Phenotype; D015995:Prevalence; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000097043:Interleukin-22
D007371:Interferon-gamma; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22